Poly and copoly(N-vinylamide)s and their use in capillary electrophoresis

ABSTRACT

The invention relates generally to polymers and copolymers comprising N-vinylamide-type monomers, their preparation, and compositions, such as electrophoresis separation media, containing the same; to supports, such as capillaries, containing these polymers; and methods for separating a mixture of biomolecules, especially polynucleotides, using capillary electrophoresis. Separation media comprising such polymers yield advantageous performance in the analysis and separation of biomolecules by capillary electrophoresis.

This application claims the benefit of U.S. provisional application No.60/471,519 filed May 15; 2003, the disclosure of the provisionalapplication being incorporated by reference herein in its entirety.

1. FIELD OF THE INVENTION

The invention relates generally to polymers and copolymers comprising aN-vinylamide-type monomer, their preparation, and compositions usefulfor electrophoresis separation comprising the same; and to supports,such as capillaries, containing these polymers and methods forseparating a mixture of biomolecules, especially polynucleotides, usingcapillary electrophoresis.

2. BACKGROUND OF THE INVENTION

Capillary electrophoresis (“CE”) is a widely used analytical methodbecause of several technical advantages that it provides, namely: (i)capillaries containing a separation medium have high surface-to-volumeratios and dissipate heat efficiently which, in turn, permitshigh-voltage fields to be used for rapid separations; (ii) minimalsample volume is needed; (iii) superior resolution is attainable; and(iv) the technique can easily be automated, e.g., Camilleri, Ed.,Capillary Electrophoresis: Theory and Practice (CRC Press, Boca Raton,1993); Grossman et al., Eds., Capillary Electrophoresis (Academic Press,San Diego, 1992). Because of these advantages, there has been greatinterest in applying CE to the separation of biomolecules, particularlyin nucleic acid analysis. The need for rapid and accurate separation ofnucleic acids, particularly deoxyribonucleic acid (“DNA”), arises in theanalysis of polymerase chain reaction products and DNA sequencingfragment analysis, e.g., Williams, Methods 4:227-232 (1992); Drossman etal., Anal. Chem., 62:900-903 (1990); Huang et al., Anal. Chem.,64:2149-2154 (1992); Swerdlow et al., Nucleic Acids Research,18:1415-1419 (1990).

There remains, however, a need for polymers and copolymers that areeffective for separating, e.g., a mixture of biomolecules, especiallypolynucleotides, using CE, and compositions comprising a polymer usefulfor the same.

The citation of any reference in Section 2 of this application is not anadmission that the reference is prior art to the application.

3. SUMMARY OF THE INVENTION

A first embodiment of the invention relates to a polymer having the formpoly(M₁ ^(x)M₂ ^(y)) and a salts thereof comprising one or more monomersof type M₁ and optionally one or more monomers of type M₂, wherein:

(a) each monomer in the polymer is of type M₁ or M₂;

(b) x is an integer ranging from 1 to 5 and represents the number ofmonomer subtypes of type M₁ that are present in the polymer;

(c) y is an integer ranging from 0 to 5 and represents the number ofmonomer subtypes of type M₂ that are present in the polymer;

(d) each monomer subtype of type M₁ in the polymer independently has theformula (I):

-   -   where each A₁ is independently ═O, ═S or ═NX₁;    -   each of R₁, R₂, R₃ and R₄ is independently —H, —(C₁-C₁₀ alkyl),        —(C₃-C₈ cycloalkyl), -(aryl), -(5- to 10-membered heteroaryl),        —(C₁-C₁₀ alkyl)(aryl) or -(aryl)(C₁-C₁₀ alkyl);    -   each R₅ is independently —(H), —(C₁-C₁₀ alkyl), —(C₁-C₁₀        heteroalkyl), —(C₃-C₈ cycloalkyl), -(3- to 8-membered        heterocycloalkyl), -(aryl), -(5- to 10-membered heteroaryl),        —(C₁-C₁₀ alkyl)(C₃-C₈ cycloalkyl), —(C₃-C₈ cycloalkyl)(C₁-C₁₀        alkyl), —(C₁-C₁₀ heteroalkyl)(C₃-C₈ cycloalkyl), —(C₃-C₈        cycloalkyl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀ alkyl)(3- to        8-membered heterocycloalkyl), -(3- to 8-membered        heterocycloalkyl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(3- to        8-membered heterocycloalkyl), -(3- to 8-membered        heterocycloalkyl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀ alkyl)(aryl),        -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(aryl),        -(aryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀ alkyl)(5- to 10-membered        heteroaryl), -(5- to 10-membered heteroaryl)(C₁-C₁₀ alkyl),        —(C₁-C₁₀ heteroalkyl)(5- to 10-membered heteroaryl), -(5- to        10-membered heteroaryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₄        alkyl)_(p)NH₂, —(C₁-C₄ alkyl)_(p)CONH₂, —(C₁-C₄ alkyl)NHCONH₂,        —(C₁-C₄ alkyl)NHCOH or —(C₁-C₄ alkyl)_(p)NHCOCH₃, where each p        is 0 or 1; and    -   each X₁ is independently —H, —(C₁-C₁₀ alkyl), —(C₃-C₈        cycloalkyl), -(aryl), -(5- to 10-membered heteroaryl), —(C₁-C₁₀        alkyl)(aryl), -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₄ alkyl)_(p)NH₂,        —(C₁-C₄ alkyl)_(p)CONH₂, —(C₁-C₄ alkyl)NHCONH₂, —(C₁-C₄        alkyl)_(p)NHCOH or —(C₁-C₄ alkyl)_(p)NHCOCH₃, where each p is 0        or 1; and        (e) when y is not zero, each monomer subtype of type M₂ in the        polymer is independently:    -   1-vinyl-pyrrolidine-2,5-dione;    -   3-vinyl-oxazolidin-2-one;    -   1-vinyl-imidazolidin-2-one;    -   4-vinyl-morpholin-3,5-dione;    -   4-vinyl-morpholin-3-one;    -   4-vinyl-morpholine;    -   2-vinyl-1,3-dioxolane;    -   2-vinylene carbonate;    -   methoxyethylene;    -   vinyl acetate;    -   vinyl alcohol;    -   a monomer of formula (II):

-   -   -   where each A₂ is independently ═O, ═S or ═NX₂;        -   each of R₆, R₇, R₈ and R₉ is independently —H, —(C₁-C₁₀            alkyl), —(C₃-C₈ cycloalkyl), -(aryl), -(5- to 10-membered            heteroaryl), —(C₁-C₁₀ alkyl)(aryl) or -(aryl)(C₁-C₁₀ alkyl);        -   each R₁₀ is independently —H, —OH, —(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl), —(C₃-C₈ cycloalkyl), -(3- to 8-membered            heterocycloalkyl), -(aryl), -(5- to 10-membered heteroaryl),            —(C₁-C₁₀ alkyl)(C₃-C₈ cycloalkyl), —(C₃-C₈            cycloalkyl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(C₃-C₈            cycloalkyl), —(C₃-C₈ cycloalkyl)(C₁-C₁₀ heteroalkyl),            —(C₁-C₁₀ alkyl)(3- to 8-membered heterocycloalkyl), -(3- to            8-membered heterocycloalkyl)(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl)(3- to 8-membered heterocycloalkyl), -(3- to            8-membered heterocycloalkyl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀            alkyl)(aryl), -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl)(aryl), -(aryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀            alkyl)(5- to 10-membered heteroaryl), -(5- to 10-membered            heteroaryl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(5- to            10-membered heteroaryl), -(5- to 10-membered            heteroaryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₄ alkyl)_(q)NH₂,            —(C₁-C₄ alkyl)_(q)CONH₂, —(C₁-C₄ alkyl)NHCONH₂, —(C₁-C₄            alkyl)NHCOH, —(C₁-C₄ alkyl)_(q)NHCOCH₃ or a group of formula            (III):

-   -   -   where B is —CH₂—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH(CH₃)—CH₂—            and —CH₂—CH(CH₃)—, and each q is 0 or 1; and        -   each X₂ is independently —H, —OH, —(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl), —(C₃-C₈ cycloalkyl), -(aryl), -(5- to            10-membered heteroaryl), —(C₁-C₁₀ alkyl)(aryl),            -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₄ alkyl)_(q)NH₂, —(C₁-C₄            alkyl)_(q)CONH₂, —(C₁-C₄ alkyl)NHCONH₂, —(C₁-C₄            alkyl)_(q)NHCOH or —(C₁-C₄ alkyl)_(q)NHCOCH₃, where each q            is 0 or 1; or

    -   mixtures thereof;        (f) provided that at least one of A₁ and A₂ is not O.

A polymer comprising at least one monomer of type M₁ and, optionally,one or more monomers of the type M₂, or a salt thereof (the polymerbeing a “polymer of the invention”) is useful for separating a mixtureof biomolecules using CE.

A second embodiment of the invention relates to a method for making apolymer of the invention, comprising the step of polymerizing at leastone M₁ monomer, defined above, optionally in the presence of one or moremonomers of type M₂, where M₂ is defined above. Thus; it is to beunderstood that a polymer of the invention can be a homopolymer or acopolymer.

A third embodiment of the invention relates to a composition comprising(a) a polymer of the invention and (b) a buffer (the composition being a“composition of the invention”).

A fourth embodiment of the invention relates to a method for making acomposition of the invention, comprising admixing (a) a polymer of theinvention and (b) a buffer.

A fifth embodiment of the invention relates to a method for separating amixture of biomolecules, comprising:

(a) contacting a composition of the invention with a mixture comprisinga biomolecule; and

(b) applying an electric field to the composition in an amountsufficient to facilitate the separation of a biomolecule from themixture.

A sixth embodiment of the invention relates to a capillary, e.g., acapillary tube, containing a composition of the invention.

These and other objects, features and advantages of the presentinvention will become better understood with reference to the followingdescription, which illustrates non-limiting embodiments of theinvention.

4. DETAILED DESCRIPTION OF THE INVENTION

The invention relates generally to a polymer of the invention,comprising an “N-vinylamide-type monomer,” i.e., a monomer of formula(I); their preparation; compositions comprising the same; and usesthereof. The invention also relates to supports, such as capillaries,containing these polymers and methods for separating a mixture ofbiomolecules, especially polynucleotides, using CE.

As used herein, a “copolymer” is a polymer comprising two or moredifferent monomeric subunits. Thus, a polymeric chain comprising threedifferent monomers (also known as a terpolymer) is included within theterm “copolymer,” as is a polymer chain comprising more than threedifferent monomeric units. As used herein, the term “polymer” includes ahomopolymer and a copolymer. Accordingly, a polymer of the invention canbe a homopolymer or a copolymer.

In polymers of the invention, x is an integer from 1 to 5 and y is aninteger from 0 to 5. In some embodiments, x is 1. In some embodiments, yis 0. In some embodiments, y is an integer from 1 to 5. Additionalembodiments are discussed elsewhere herein.

It is to be understood that a polymer of the invention can comprise: (a)monomers of a single monomer subtype, e.g., a polymer having the formpoly(M₁ ¹M₂ ⁰) (or poly(M₁ ¹)), that is, an M₁ homopolymer; (b) monomersselected from more than one subtype of M₁, e.g., a polymer having theform poly(M₁ ²M₂ ⁰) (or poly(M₁ ²)) is an M₁ copolymer containingmonomers of a first subtype of M₁ and also monomers of a second subtypeof M₁; and (c) monomers of one or more monomer subtypes of type M₁ andmonomers of one or more monomer subtypes of type M₂, e.g., a polymerhaving the form poly(M₁ ²M₂ ¹) contains two monomer subtypes of type M₁and one monomer subtype of type M₂, that is, an M₁/M₂ copolymer.

Copolymers can be formed using many ways known to those skilled in theart, for example: by copolymerization of two or more different monomers,which copolymerization can be of the random type, the alternating typeor intermediate between these two types, i.e., “intermediate-type”; byblock copolymerization; by graft copolymerization, e.g., where anexisting polymer chain is further reacted with a different monomer; andby a post-polymerization reaction, e.g., where a polymer's ester sidegroups are partially hydrolyzed. A copolymer is conventionally known as“random” or “ideal” when a radical formed from either monomer unit atthe end of the growing polymer chain has about the same preference foradding either of the monomers and as “alternating” when a radical formedfrom one monomer at the end of the growing polymer chain prefers to addto the other monomer. See, e.g., F. W. Billmeyer, Jr., Textbook ofPolymer Science 330-331 (Wiley-Interscience, New York, 2^(nd) ed. 1971).

The IUPAC source-based nomenclature for copolymers uses the prefix“poly” followed by the names of the monomers connected by a termsignifying the arrangement of the monomers. The connector “-co-” iscommonly used and signifies a copolymer of the monomers where theirarrangement is unspecified. See C. A. Costello and D. N. Schulz,Copolymers in Kirk-Othmer Encyc. of Chem. Technol. Vol. 7, 350 (4^(th)ed. 1993). For example, poly(N-vinylamide-co-4-vinyl-morpholine) denotesa copolymer comprising N-vinylamide and 4-vinyl-morpholine monomer unitsand includes random-type, alternating-type and intermediate-typecopolymers. Similarly, poly(N-vinylamide-co-vinylacetate-co-N-butoxymethyl-methacrylamide) denotes a copolymer comprisingN-vinylamide, vinyl acetate and N-butoxymethyl-methacrylamide monomerunits and includes random-type, alternating-type and intermediate-typecopolymers. Likewise,poly(N-vinylamide-co-N-methyl-N-vinylacetamide-co-N-butoxymethyl-methacrylamide)denotes a copolymer comprising N-vinylamide, N-methyl-N-vinylacetamideand N-butoxymethyl-methacrylamide monomer units and includesrandom-type, alternating-type and intermediate-type copolymers.

4.1. Polymers of the Invention

The first embodiment of the invention relates to a polymer of theinvention having the form poly(M₁ ^(x)M₂ ^(y)), or a salt thereof,comprising one or more monomers of type M₁ and optionally one or moremonomers of type M₂, wherein:

(a) each monomer in the polymer is of type M₁ or M₂;

(b) x is an integer ranging from 1 to 5 and represents the number ofmonomer subtypes of type M₁ that are present in the polymer;

(c) y is an integer ranging from 0 to 5 and represents the number ofmonomer subtypes of type M₂ that are present in the polymer;

(d) each monomer subtype of type M₁ in the polymer independently has theformula (I):

-   -   where each A₁ is independently ═O, ═S or ═NX₁;    -   each of R₁, R₂, R₃ and R₄ is independently H, —(C₁-C₁₀ alkyl),        —(C₃-C₈ cycloalkyl), -(aryl), -(5- to 10-membered heteroaryl),        —(C₁-C₁₀ alkyl)(aryl) or -(aryl)(C₁-C₁₀ alkyl);    -   each R₅ is independently —(H), —(C₁-C₁₀ alkyl), —(C₁-C₁₀        heteroalkyl), —(C₃-C₈ cycloalkyl), -(3- to 8-membered        heterocycloalkyl), -(aryl), -(5- to 10-membered heteroaryl),        —(C₁-C₁₀ alkyl)(C₃-C₈ cycloalkyl), —(C₃-C₈ cycloalkyl)(C₁-C₁₀        alkyl), —(C₁-C₁₀ heteroalkyl)(C₃-C₈ cycloalkyl), —(C₃-C₈        cycloalkyl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀ alkyl)(3- to        8-membered heterocycloalkyl), -(3- to 8-membered        heterocycloalkyl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(3- to        8-membered heterocycloalkyl), -(3- to 8-membered        heterocycloalkyl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀ alkyl)(aryl),        -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(aryl),        -(aryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀ alkyl)(5- to 10-membered        heteroaryl), -(5- to 10-membered heteroaryl)(C₁-C₁₀ alkyl),        —(C₁-C₁₀ heteroalkyl)(5- to 10-membered heteroaryl), -(5- to        10-membered heteroaryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₄        alkyl)_(p)NH₂, —(C₁-C₄ alkyl)_(p)CONH₂, —(C₁-C₄ alkyl)NHCONH₂,        —(C₁-C₄ alkyl)NHCOH or —(C₁-C₄ alkyl)_(p)NHCOCH₃, where each p        is 0 or 1; and    -   each X₁ is independently —H, —(C₁-C₁₀ alkyl), —(C₃-C₈        cycloalkyl), -(aryl), -(5- to 10-membered heteroaryl), —(C₁-C₁₀        alkyl)(aryl), -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₄ alkyl)_(p)NH₂,        —(C₁-C₄ alkyl)_(p)CONH₂, —(C₁-C₄ alkyl)NHCONH₂, —(C₁-C₄        alkyl)_(p)NHCOH or —(C₁-C₄ alkyl)_(p)NHCOCH₃, where each p is 0        or 1; and        (e) when y is not zero, each monomer subtype of type M₂ in the        polymer is independently:    -   1-vinyl-pyrrolidine-2,5-dione;    -   3-vinyl-oxazolidin-2-one;    -   1-vinyl-imidazolidin-2-one;    -   4-vinyl-morpholin-3,5-dione;    -   4-vinyl-morpholin-3-one;    -   4-vinyl-morpholine;    -   2-vinyl-1,3-dioxolane;    -   2-vinylene carbonate;    -   methoxyethylene;    -   vinyl acetate;    -   vinyl alcohol;    -   a monomer of formula (II):

-   -   -   where each A₂ is independently ═O, ═S or ═NX₂;        -   each of R₆, R₇, R₈ and R₉ is independently —H, —(C₁-C₁₀            alkyl), —(C₃-C₈ cycloalkyl), -(aryl), -(5- to 10-membered            heteroaryl), —(C₁-C₁₀ alkyl)(aryl) or -(aryl)(C₁-C₁₀ alkyl);        -   each R₁₀ is independently —H, —OH, —(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl), —(C₃-C₈ cycloalkyl), -(3- to            8-membered-heterocycloalkyl), -(aryl), -(5- to 10-membered            heteroaryl), —(C₁-C₁₀ alkyl)(C₃-C₈ cycloalkyl), —(C₃-C₈            cycloalkyl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(C₃-C₈            cycloalkyl), —(C₃-C₈ cycloalkyl)(C₁-C₁₀ heteroalkyl),            —C₁-C₁₀ alkyl)(3- to 8-membered heterocycloalkyl), -(3- to            8-membered heterocycloalkyl)(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl)(3- to 8-membered heterocycloalkyl), -(3- to            8-membered heterocycloalkyl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀            alkyl)(aryl), -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl)(aryl), -(aryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀            alkyl)(5- to 10-membered heteroaryl), -(5- to 10-membered            heteroaryl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(5- to            10-membered heteroaryl), -(5- to 10-membered            heteroaryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₄ alkyl)_(q)NH₂,            —(C₁-C₄ alkyl)_(q)CONH₂, —(C₁-C₄ alkyl)NHCONH₂, —(C₁-C₄            alkyl)NHCOH, —(C₁-C₄ alkyl)_(q)NHCOCH₃ or a group of formula            (III):

-   -   -   where B is —CH₂—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH(CH₃)—CH₂—            and —CH₂—CH(CH₃)—, and each q is 0 or 1; and        -   each X₂ is independently —H, —OH, —(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl), —(C₃-C₈ cycloalkyl), -(aryl), -(5- to            10-membered heteroaryl), —(C₁-C₁₀ alkyl)(aryl),            -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₄ alkyl)_(q)NH₂, (C₁-C₄            alkyl)_(q)CONH₂, —(C₁-C₄ alkyl)NHCONH₂, —(C₁-C₄            alkyl)_(q)NHCOH or —(C₁-C₄ alkyl)_(q)NHCOCH₃, where each q            is 0 or 1; or

    -   mixtures thereof;        (f) provided that at least one of A₁ and A₂ is not O.

In certain embodiments, x is 1 and y is 0.

In certain embodiments, x is 2 and y is 0.

In certain embodiments, x is 3 and y is 0.

In certain embodiments, x is 4 and y is 0.

In certain embodiments, x is 5 and y is 0.

In certain embodiments, x is 1 and y is 1.

In certain embodiments, x is 2 and y is 1.

In certain embodiments, x is 3 and y is 1.

In certain embodiments, x is 4 and y is 1.

In certain embodiments, x is 5 and y is 1.

In certain embodiments, x is 1 and y is 2.

In certain embodiments, x is 2 and y is 2.

In certain embodiments, x is 3 and y is 2.

In certain embodiments, x is 4 and y is 2.

In certain embodiments, x is 5 and y is 2.

In certain embodiments, x is 1 and y is 3.

In certain embodiments, x is 2 and y is 3.

In certain embodiments, x is 3 and y is 3.

In certain embodiments, x is 4 and y is 3.

In certain embodiments, x is 5 and y is 3.

In certain embodiments, x is 1 and y is 4.

In certain embodiments, x is 2 and y is 4.

In certain embodiments, x is 3 and y is 4.

In certain embodiments, x is 4 and y is 4.

In certain embodiments, x is 5 and y is 4.

In certain embodiments, x is 1 and y is 5.

In certain embodiments, x is 2 and y is 5.

In certain embodiments, x is 3 and y is 5.

In certain embodiments, x is 4 and y is 5.

In certain embodiments, x is 5 and y is 5.

In certain embodiments, y is 0 and, for each monomer subtype of type M₁:

-   -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl.

In other embodiments y is 0 and, for each monomer subtype of type M₁:

-   -   R₁ and R₂ are H;    -   each R₃, R₄ and R₅ is independently H or methyl.

In another embodiment, y is 0 and, for each monomer subtype of type M₁:

-   -   R₁, R₂, R₃, R₄ and R₅ are H.

In another embodiment, y is 0 and, for each monomer subtype of type M₁:

-   -   R₁, R₂, R₃, and R₄ are H; and    -   R₅ is methyl.

In another embodiment, y is 0 and, for each monomer subtype of type M₁:

-   -   R₁, R₂ and R₃ are H; and    -   R₄ and R₅ are methyl.

In certain embodiments, y is 0, x is 2 and, for each monomer subtype oftype M₁:

-   -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl.

In other embodiments, y is 0, x is 2 and, for each monomer subtype oftype M₁:

-   -   R₁ and R₂ are H;    -   each R₃, R₄ and R₅ is independently H or methyl.

In another embodiment, y is 0, x is 2 and, for each monomer subtype oftype M₁:

-   -   R₁, R₂, R₃, R₄ and R₅ are H.

In another embodiment, y is 0, x is 2 and, for each monomer subtype oftype M₁:

-   -   R₁, R₂, R₃, and R₄ are H; and    -   R₅ is methyl.

In another embodiment, y is 0, x is 2 and, for each monomer subtype oftype M₁:

-   -   R₁, R₂ and R₃ are H; and    -   R₄ and R₅ are methyl.

In certain embodiments, y is 0, x is 1 and, for M₁:

-   -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl.

In other embodiments, y is 0, x is 1 and, for M₁:

-   -   R₁ and R₂ are H;    -   each R₃, R₄ and R₅ is independently H or methyl.

In another embodiment, y is 0, x is 1 and, for M₁:

-   -   R₁, R₂, R₃, R₄ and R₅ are H.

In another embodiment, y is 0, x is 1 and, for M₁:

-   -   R₁, R₂, R₃, and R₄ are H; and    -   R₅ is methyl.

In another embodiment, y is 0, x is 1 and, for M₁:

-   -   R₁, R₂ and R₃ are H; and    -   R₄ and R₅ are methyl.

In certain embodiments:

(a) for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (b) y is 2; and        (c) for each monomer subtype of type M₂ of formula (II):    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In certain embodiments:

(a) for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (b) y is 1; and        (c) for M₂ of formula (II):    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In certain embodiments:

(a) x is 2;

(b) for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (c) y is 2; and        (d) for each monomer subtype of type M₂ of formula (II):    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In certain embodiments:

(a) x is 2;

(b) for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (c) y is 1; and        (d) for M₂ of formula (II):    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In certain embodiments:

(a) x is 1;

(b) for M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (c) y is 2; and        (d) for each monomer subtype of type M₂ of formula (II):    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In certain embodiments:

(a) x is 1;

(b) for M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (c) y is 1; and        (d) for M₂ of formula (II):    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In some embodiments, M₁, or each monomer subtype of type M₁ if x>1, isN-vinylformamide, N-vinylacetamide, N-vinylpropamide, N-vinylbutamide,N-vinylpentamide, N-vinylhexamide, N-vinylheptamide, N-vinyloctamide,N-vinylnonamide, N-vinyldecamide, N-methyl-N-vinylformamide,N-methyl-N-vinylacetamide, N-methyl-N-vinylpropamide,N-methyl-N-vinylbutamide, N-methyl-N-vinylpentamide,N-methyl-N-vinylhexamide, N-methyl-N-vinylheptamide,N-methyl-N-vinyloctamide, N-methyl-N-vinylnonamide,N-methyl-N-vinyldecamide, N-ethyl-N-vinylformamide,N-ethyl-N-vinylacetamide, N-ethyl-N-vinylpropamide,N-ethyl-N-vinylbutamide, N-ethyl-N-vinylpentamide,N-ethyl-N-vinylhexamide, N-ethyl-N-vinylheptamide,N-ethyl-N-vinyloctamide, N-ethyl-N-vinylnonamide,N-ethyl-N-vinyldecamide, N-n-propyl-N-vinylformamide,N-n-propyl-N-vinylacetamide, N-n-propyl-N-vinylpropamide,N-n-propyl-N-vinylbutamide, N-n-propyl-N-vinylpentamide,N-n-propyl-N-vinylhexamide, N-n-propyl-N-vinylheptamide,N-n-propyl-N-vinyloctamide, N-n-propyl-N-vinylnonamide,N-n-propyl-N-vinyldecamide, N-iso-propyl-N-vinylformamide,N-iso-propyl-N-vinylacetamide, N-iso-propyl-N-vinylpropamide,N-iso-propyl-N-vinylbutamide, N-iso-propyl-N-vinylpentamide,N-iso-propyl-N-vinylhexamide, N-iso-propyl-N-vinylheptamide,N-iso-propyl-N-vinyloctamide, N-iso-propyl-N-vinylnonamide,N-iso-propyl-N-vinyldecamide, or a mixture thereof.

In some embodiments, M₁, or each monomer subtype of type M₁ if x>1, isN-vinylformamide, N-vinylacetamide, N-vinylpropamide, N-vinylbutamide,N-methyl-N-vinylformamide, N-methyl-N-vinylacetamide,N-methyl-N-vinylpropamide, N-methyl-N-vinylbutamide,N-ethyl-N-vinylformamide, N-ethyl-N-vinylacetamide,N-ethyl-N-vinylpropamide, N-ethyl-N-vinylbutamide,N-n-propyl-N-vinylformamide, N-n-propyl-N-vinylacetamide,N-n-propyl-N-vinylpropamide, N-n-propyl-N-vinylbutamide,N-iso-propyl-N-vinylformamide, N-iso-propyl-N-vinylacetamide,N-iso-propyl-N-vinylpropamide, N-iso-propyl-N-vinylbutamide, or amixture thereof.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, isN-hydroxy-acrylamide, N-methoxy-acrylamide, acryloyl urea,1-vinyl-pyrrolidine-2,5-dione, 3-vinyl-oxazolidin-2-one,1-vinyl-imidazolidin-2-one, 4-vinyl-morpholin-3,5-dione,4-vinyl-morpholin-3-one, 4-vinyl-morpholine, 2-vinyl-1,3-dioxolane,2-vinylene carbonate, methoxyethylene, vinyl acetate, vinyl alcohol, ora mixture thereof.

It is conventional to prepare polymers or copolymers containing vinylalcohol monomer units using indirect methods. For example, polymerscontaining vinyl alcohol monomer units can be prepared by performing atleast a partial alcoholysis of poly(vinyl acetate), e.g., by usingmethanol or ethanol with an acid or base catalyst. See, e.g., F. W.Billmeyer, Jr., Textbook of Polymer Science, 416 (2^(nd) ed. 1971). Thealcoholysis is carried out conventionally, e.g., by dissolving orsuspending poly(vinyl acetate) in the alcohol selected, adding thecatalyst, and optionally heating.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, isacrylamide, N-acetamido-acrylamide, N-acetyl-acrylamide,N-allyl-acrylamide, N-2-aminoethyl-acrylamide hydrochloride,N-2-aminoethyl-N-methyl-acrylamide hydrochloride,N-3-aminopropyl-acrylamide hydrochloride,N-3-aminopropyl-N-methyl-acrylamide hydrochloride,N-butoxymethyl-acrylamide, N-n-butyl-acrylamide,N-tert-butyl-acrylamide, N-2-cyanoethyl-acrylamide,N-cyanomethyl-acrylamide, N-cyanomethyl-N-methyl-acrylamide,N,N-diallyl-acrylamide, N,N-diethyl-acrylamide,N,N-diisopropyl-acrylamide, N,N-dimethyl-acrylamide,N,N′-ethylene-bis-acrylamide, N-ethyl-N-methyl-acrylamide,N-ethyl-N-propyl-acrylamide, N-2-glycolic acid-acrylamide, N-2-glycolicacid methyl ester-acrylamide, N-2-hydroxyethyl-acrylamide,N-2-hydroxyethyl-N-methyl-acrylamide, N-hydroxymethyl-acrylamide,N-hydroxymethyl-N-methyl-acrylamide, N-iso-propyl-acrylamide,N,N′-iso-propylene-bis-acrylamide, N-2-methoxyethyl-acrylamide,N-methoxymethyl-acrylamide, N-methyl-acrylamide,N,N′-methylene-bis-acrylamide,N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)methyl-acrylamide,N-tri(hydroxymethyl)methyl-N-methyl-acrylamide, N,N′-trimethylene-bis-acrylamide, N-3-(trimethylammonium)propyl-acrylamidehydrochloride, N-3-(trimethylammonium)propyl-N-methyl-acrylamidehydrochloride, or a mixture thereof.

In embodiments where for M₂, R₁₀ is a group of formula (III), such as inthe monomer unit N,N′-trimethylene-bis-acrylamide, the group B informula (III) is methylene, ethylene, trimethylene and isopropylene. Inthis context, for the purposes of this application, “methylene”signifies the B group —CH₂—, “ethylene” signifies the B group —CH₂—CH₂—,“trimethylene” signifies the B group —CH₂—CH₂—CH₂—, and “isopropylene”signifies the B groups —CH(CH₃)—CH₂— and —CH₂—CH(CH₃)—.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, isacrylamide, N-acetamido-acrylamide, N-acetyl-acrylamide,N-allyl-acrylamide, N-2-aminoethyl-acrylamide hydrochloride,N-2-aminoethyl-N-methyl-acrylamide hydrochloride,N-3-aminopropyl-acrylamide hydrochloride,N-3-aminopropyl-N-methyl-acrylamide hydrochloride,N-butoxymethyl-acrylamide, N-n-butyl-acrylamide,N-tert-butyl-acrylamide, N-2-cyanoethyl-acrylamide,N-cyanomethyl-acrylamide, N-cyanomethyl-N-methyl-acrylamide,N,N-diallyl-acrylamide, N,N-diethyl-acrylamide,N,N-diisopropyl-acrylamide, N,N-dimethyl-acrylamide,N-ethyl-N-methyl-acrylamide, N-ethyl-N-propyl-acrylamide, N-2-glycolicacid-acrylamide, N-2-glycolic acid methyl ester-acrylamide,N-2-hydroxyethyl-acrylamide, N-2-hydroxyethyl-N-methyl-acrylamide,N-hydroxymethyl-acrylamide, N-hydroxymethyl-N-methyl-acrylamide,N-iso-propyl-acrylamide, N-2-methoxyethyl-acrylamide,N-methoxymethyl-acrylamide, N-methyl-acrylamide,N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)methyl-acrylamide,N-tri(hydroxymethyl)methyl-N-methyl-acrylamide,N-3-(trimethylammonium)propyl-acrylamide hydrochloride,N-3-(trimethylammonium)propyl-N-methyl-acrylamide hydrochloride, or amixture thereof.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, ismethacrylamide, N-acetamido-methacrylamide, N-acetyl-methacrylamide,N-allyl-methacrylamide, N-2-aminoethyl-methacrylamide hydrochloride,N-3-aminopropyl-methacrylamide hydrochloride,N-butoxymethyl-methacrylamide, N-n-butyl-methacrylamide,N-tert-butyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N-cyanomethyl-methacrylamide, N-cyanomethyl-N-methyl-methacrylamide,N,N-diethyl-methacrylamide, N,N-dimethyl-methacrylamide, N-2-glycolicacid-methacrylamide, N-2-hydroxyethyl-methacrylamide,N-hydroxymethyl-methacrylamide, N-hydroxymethyl-N-methyl-methacrylamide,N-iso-propyl-methacrylamide, N,N′-iso-propylene-bis-methacrylamide,N-2-methoxyethyl-methacrylamide, N-methoxymethyl-methacrylamide,N-methyl-methacrylamide, N,N′-methylene-bis-methacrylamide,N-tri(hydroxymethyl)methyl-methacrylamide,N,N′-trimethylene-bis-methacrylamide,N-3-(trimethylammonium)propyl-methacrylamide hydrochloride, or a mixturethereof.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, ismethacrylamide, N-acetamido-methacrylamide, N-acetyl-methacrylamide,N-allyl-methacrylamide, N-2-aminoethyl-methacrylamide hydrochloride,N-3-aminopropyl-methacrylamide hydrochloride,N-butoxymethyl-methacrylamide, N-n-butyl-methacrylamide,N-tert-butyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N-cyanomethyl-methacrylamide, N-cyanomethyl-N-methyl-methacrylamide,N,N-diethyl-methacrylamide, N,N-dimethyl-methacrylamide, N-2-glycolicacid-methacrylamide, N-2-hydroxyethyl-methacrylamide,N-hydroxymethyl-methacrylamide, N-hydroxymethyl-N-methyl-methacrylamide,N-iso-propyl-methacrylamide, N-2-methoxyethyl-methacrylamide,N-methoxymethyl-methacrylamide, N-methyl-methacrylamide,N-tri(hydroxymethyl)methyl-methacrylamide,N-3-(trimethylammonium)propyl-methacrylamide hydrochloride, or a mixturethereof.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, isacrylamide, N-acetamido-acrylamide, N-acetyl-acrylamide,N-allyl-acrylamide, N-2-aminoethyl-acrylamide hydrochloride,N-2-aminoethyl-N-methyl-acrylamide hydrochloride,N-3-aminopropyl-acrylamide hydrochloride,N-3-aminopropyl-N-methyl-acrylamide hydrochloride,N-butoxymethyl-acrylamide, N-n-butyl-acrylamide,N-tert-butyl-acrylamide, N-2-cyanoethyl-acrylamide,N-cyanomethyl-acrylamide, N-cyanomethyl-N-methyl-acrylamide,N,N-diallyl-acrylamide, N,N-diethyl-acrylamide,N,N-diisopropyl-acrylamide, N,N-dimethyl-acrylamide,N,N′-ethylene-bis-acrylamide, N-ethyl-N-methyl-acrylamide,N-ethyl-N-propyl-acrylamide, N-2-glycolic acid-acrylamide, N-2-glycolicacid methyl ester-acrylamide, N-2-hydroxyethyl-acrylamide,N-2-hydroxyethyl-N-methyl-acrylamide, N-hydroxymethyl-acrylamide,N-hydroxymethyl-N-methyl-acrylamide, N-iso-propyl-acrylamide,N,N′-iso-propylene-bis-acrylamide, N-2-methoxyethyl-acrylamide,N-methoxymethyl-acrylamide, N-methyl-acrylamide, N,N′-methylene-bis-acrylamide,N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)methyl-acrylamide,N-tri(hydroxymethyl)methyl-N-methyl-acrylamide,N,N′-trimethylene-bis-acrylamide,N-3-(trimethylammonium)propyl-acrylamide hydrochloride,N-3-(trimethylammonium)propyl-N-methyl-acrylamide hydrochloride,methacrylamide, N-acetamido-methacrylamide, N-acetyl-methacrylamide,N-allyl-methacrylamide, N-2-aminoethyl-methacrylamide hydrochloride,N-3-aminopropyl-methacrylamide hydrochloride,N-butoxymethyl-methacrylamide, N-n-butyl-methacrylamide,N-tert-butyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N-cyanomethyl-methacrylamide, N-cyanomethyl-N-methyl-methacrylamide,N,N-diethyl-methacrylamide, N,N-dimethyl-methacrylamide, N-2-glycolicacid-methacrylamide, N-2-hydroxyethyl-methacrylamide,N-hydroxymethyl-methacrylamide, N-hydroxymethyl-N-methyl-methacrylamide,N-iso-propyl-methacrylamide, N,N′-iso-propylene-bis-methacrylamide,N-2-methoxyethyl-methacrylamide, N-methoxymethyl-methacrylamide,N-methyl-methacrylamide, N,N′-methylene-bis-methacrylamide,N-tri(hydroxymethyl)methyl-methacrylamide,N,N′-trimethylene-bis-methacrylamide,N-3-(trimethylammonium)propyl-methacrylamide hydrochloride, or a mixturethereof.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, isacrylamide, N-acetamido-acrylamide, N-acetyl-acrylamide,N-allyl-acrylamide, N-2-aminoethyl-acrylamide hydrochloride,N-2-aminoethyl-N-methyl-acrylamide hydrochloride,N-3-aminopropyl-acrylamide hydrochloride,N-3-aminopropyl-N-methyl-acrylamide hydrochloride,N-butoxymethyl-acrylamide, N-n-butyl-acrylamide,N-tert-butyl-acrylamide, N-2-cyanoethyl-acrylamide,N-cyanomethyl-acrylamide, N-cyanomethyl-N-methyl-acrylamide,N,N-diallyl-acrylamide, N,N-diethyl-acrylamide,N,N-diisopropyl-acrylamide, N,N-dimethyl-acrylamide,N-ethyl-N-methyl-acrylamide, N-ethyl-N-propyl-acrylamide, N-2-glycolicacid-acrylamide, N-2-glycolic acid methyl ester-acrylamide,N-2-hydroxyethyl-acrylamide, N-2-hydroxyethyl-N-methyl-acrylamide,N-hydroxymethyl-acrylamide, N-hydroxymethyl-N-methyl-acrylamide,N-iso-propyl-acrylamide, N-2-methoxyethyl-acrylamide,N-methoxymethyl-acrylamide, N-methyl-acrylamide,N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)methyl-acrylamide,N-tri(hydroxymethyl)methyl-N-methyl-acrylamide,N-3-(trimethylammonium)propyl-acrylamide hydrochloride,N-3-(trimethylammonium)propyl-N-methyl-acrylamide hydrochloride,methacrylamide, N-acetamido-methacrylamide, N-acetyl-methacrylamide,N-allyl-methacrylamide, N-2-aminoethyl-methacrylamide hydrochloride,N-3-aminopropyl-methacrylamide hydrochloride,N-butoxymethyl-methacrylamide, N-n-butyl-methacrylamide,N-tert-butyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N-cyanomethyl-methacrylamide, N-cyanomethyl-N-methyl-methacrylamide,N,N-diethyl-methacrylamide, N,N-dimethyl-methacrylamide, N-2-glycolicacid-methacrylamide, N-2-hydroxyethyl-methacrylamide,N-hydroxymethyl-methacrylamide, N-hydroxymethyl-N-methyl-methacrylamide,N-iso-propyl-methacrylamide, N-2-methoxyethyl-methacrylamide,N-methoxymethyl-methacrylamide, N-methyl-methacrylamide,N-tri(hydroxymethyl)methyl-methacrylamide,N-3-(trimethylammonium)propyl-methacrylamide hydrochloride, or a mixturethereof.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, isN-acetamido-acrylamide, N-acetyl-acrylamide, N-allyl-acrylamide,N-2-aminoethyl-acrylamide hydrochloride,N-2-aminoethyl-N-methyl-acrylamide hydrochloride,N-3-aminopropyl-acrylamide hydrochloride,N-3-aminopropyl-N-methyl-acrylamide hydrochloride,N-butoxymethyl-acrylamide, N-n-butyl-acrylamide,N-2-cyanoethyl-acrylamide, N-cyanomethyl-acrylamide,N-cyanomethyl-N-methyl-acrylamide, N,N-diallyl-acrylamide,N,N-diisopropyl-acrylamide, N-ethyl-N-methyl-acrylamide,N-ethyl-N-propyl-acrylamide, N-2-glycolic acid-acrylamide, N-2-glycolicacid methyl ester-acrylamide, N-2-hydroxyethyl-acrylamide,N-2-hydroxyethyl-N-methyl-acrylamide, N-hydroxymethyl-acrylamide,N-hydroxymethyl-N-methyl-acrylamide, N-2-methoxyethyl-acrylamide,N-methoxymethyl-acrylamide, N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)methyl-acrylamide,N-tri(hydroxymethyl)methyl-N-methyl-acrylamide,N-3-(trimethylammonium)propyl-acrylamide hydrochloride,N-3-(trimethylammonium)propyl-N-methyl-acrylamide hydrochloride,N-acetamido-methacrylamide, N-acetyl-methacrylamide,N-allyl-methacrylamide, N-2-aminoethyl-methacrylamide hydrochloride,N-3-aminopropyl-methacrylamide hydrochloride,N-butoxymethyl-methacrylamide, N-n-butyl-methacrylamide,N-tert-butyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N-cyanomethyl-methacrylamide, N-cyanomethyl-N-methyl-methacrylamide,N,N-diethyl-methacrylamide, N,N-dimethyl-methacrylamide, N-2-glycolicacid-methacrylamide, N-2-hydroxyethyl-methacrylamide,N-hydroxymethyl-methacrylamide, N-hydroxymethyl-N-methyl-methacrylamide,N-iso-propyl-methacrylamide, N-2-methoxethyl-methacrylamide,N-methoxymethyl-methacrylamide, N-methyl-methacrylamide,N-tri(hydroxymethyl)methyl-methacrylamide,N-3-(trimethylammonium)propyl-methacrylamide hydrochloride, or a mixturethereof.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, isN-hydroxy-acrylamide, N-methoxy-acrylamide, acryloyl urea,1-vinyl-pyrrolidine-2,5-dione, 3-vinyl-oxazolidin-2-one,1-vinyl-imidazolidin-2-one, 4-vinyl-morpholin-3,5-dione,4-vinyl-morpholin-3-one, 4-vinyl-morpholine, 2-vinyl-1,3-dioxolane,2-vinylene carbonate, methoxyethylene, vinyl acetate, vinyl alcohol,acrylamide, N-acetamido-acrylamide, N-acetyl-acrylamide,N-allyl-acrylamide, N-2-aminoethyl-acrylamide hydrochloride,N-2-aminoethyl-N-methyl-acrylamide hydrochloride,N-3-aminopropyl-acrylamide hydrochloride,N-3-aminopropyl-N-methyl-acrylamide hydrochloride,N-butoxymethyl-acrylamide, N-n-butyl-acrylamide,N-tert-butyl-acrylamide, N-2-cyanoethyl-acrylamide,N-cyanomethyl-acrylamide, N-cyanomethyl-N-methyl-acrylamide,N,N-diallyl-acrylamide, N,N-diethyl-acrylamide,N,N-diisopropyl-acrylamide, N,N-dimethyl-acrylamide,N,N′-ethylene-bis-acrylamide, N-ethyl-N-methyl-acrylamide,N-ethyl-N-propyl-acrylamide, N-2-glycolic acid-acrylamide, N-2-glycolicacid methyl ester-acrylamide, N-2-hydroxyethyl-acrylamide,N-2-hydroxyethyl-N-methyl-acrylamide, N-hydroxymethyl-acrylamide,N-hydroxymethyl-N-methyl-acrylamide, N-iso-propyl-acrylamide,N,N′-iso-propylene-bis-acrylamide, N-2-methoxyethyl-acrylamide,N-methoxymethyl-acrylamide, N-methyl-acrylamide,N,N′-methylene-bis-acrylamide,N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)methyl-acrylamide,N-tri(hydroxymethyl)methyl-N-methyl-acrylamide,N,N′-trimethylene-bis-acrylamide,N-3-(trimethylammonium)propyl-acrylamide hydrochloride,N-3-(trimethylammonium)propyl-N-methyl-acrylamide hydrochloride,methacrylamide, N-acetamido-methacrylamide, N-acetyl-methacrylamide,N-allyl-methacrylamide, N-2-aminoethyl-methacrylamide hydrochloride,N-3-aminopropyl-methacrylamide hydrochloride,N-butoxymethyl-methacrylamide, N-n-butyl-methacrylamide,N-tert-butyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N-cyanomethyl-methacrylamide, N-cyanomethyl-N-methyl-methacrylamide,N,N-diethyl-methacrylamide, N,N-dimethyl-methacrylamide, N-2-glycolicacid-methacrylamide, N-2-hydroxyethyl-methacrylamide,N-hydroxymethyl-methacrylamide, N-hydroxymethyl-N-methyl-methacrylamide,N-iso-propyl-methacrylamide, N,N′-iso-propylene-bis-methacrylamide,N-2-methoxethyl-methacrylamide, N-methoxymethyl-methacrylamide,N-methyl-methacrylamide, N,N′-methylene-bis-methacrylamide,N-tri(hydroxymethyl)methyl-methacrylamide,N,N′-trimethylene-bis-methacrylamide,N-3-(trimethylammonium)propyl-methacrylamide hydrochloride, or a mixturethereof.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, isN-hydroxy-acrylamide, N-methoxy-acrylamide, acryloyl urea,1-vinyl-pyrrolidine-2,5-dione, 3-vinyl-oxazolidin-2-one,1-vinyl-imidazolidin-2-one, 4-vinyl-morpholin-3,5-dione,4-vinyl-morpholin-3-one, 4-vinyl-morpholine, 2-vinyl-1,3-dioxolane,2-vinylene carbonate, methoxyethylene, vinyl acetate, vinyl alcohol,acrylamide, N-acetamido-acrylamide, N-acetyl-acrylamide,N-allyl-acrylamide, N-2-aminoethyl-acrylamide hydrochloride,N-2-aminoethyl-N-methyl-acrylamide hydrochloride,N-3-aminopropyl-acrylamide hydrochloride,N-3-aminopropyl-N-methyl-acrylamide hydrochloride,N-butoxymethyl-acrylamide, N-n-butyl-acrylamide,N-tert-butyl-acrylamide, N-2-cyanoethyl-acrylamide,N-cyanomethyl-acrylamide, N-cyanomethyl-N-methyl-acrylamide,N,N-diallyl-acrylamide, N,N-diethyl-acrylamide,N,N-diisopropyl-acrylamide, N,N-dimethyl-acrylamide,N-ethyl-N-methyl-acrylamide, N-ethyl-N-propyl-acrylamide, N-2-glycolicacid-acrylamide, N-2-glycolic acid methyl ester-acrylamide,N-2-hydroxyethyl-acrylamide, N-2-hydroxyethyl-N-methyl-acrylamide,N-hydroxymethyl-acrylamide, N-hydroxymethyl-N-methyl-acrylamide,N-iso-propyl-acrylamide, N-2-methoxyethyl-acrylamide,N-methoxymethyl-acrylamide, N-methyl-acrylamide,N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)methyl-acrylamide,N-tri(hydroxymethyl)methyl-N-methyl-acrylamide,N-3-(trimethylammonium)propyl-acrylamide hydrochloride,N-3-(trimethylammonium)propyl-N-methyl-acrylamide hydrochloride,methacrylamide, N-acetamido-methacrylamide, N-acetyl-methacrylamide,N-allyl-methacrylamide, N-2-aminoethyl-methacrylamide hydrochloride,N-3-aminopropyl-methacrylamide hydrochloride,N-butoxymethyl-methacrylamide, N-n-butyl-methacrylamide,N-tert-butyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N-cyanomethyl-methacrylamide, N-cyanomethyl-N-methyl-methacrylamide,N,N-diethyl-methacrylamide, N,N-dimethyl-methacrylamide, N-2-glycolicacid-methacrylamide, N-2-hydroxyethyl-methacrylamide,N-hydroxymethyl-methacrylamide, N-hydroxymethyl-N-methyl-methacrylamide,N-iso-propyl-methacrylamide, N-2-methoxyethyl-methacrylamide,N-methoxymethyl-methacrylamide, N-methyl-methacrylamide,N-tri(hydroxymethyl)methyl-methacrylamide,N-3-(trimethylammonium)propyl-methacrylamide hydrochloride, or a mixturethereof.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, isN-hydroxy-acrylamide, N-methoxy-acrylamide, acryloyl urea,1-vinyl-pyrrolidine-2,5-dione, 3-vinyl-oxazolidin-2-one,1-vinyl-imidazolidin-2-one, 4-vinyl-morpholin-3,5-dione,4-vinyl-morpholin-3-one, 4-vinyl-morpholine, 2-vinylene carbonate,methoxyethylene, N-acetamido-acrylamide, N-acetyl-acrylamide,N-allyl-acrylamide, N-2-aminoethyl-acrylamide hydrochloride,N-2-aminoethyl-N-methyl-acrylamide hydrochloride,N-3-aminopropyl-acrylamide hydrochloride,N-3-aminopropyl-N-methyl-acrylamide hydrochloride,N-butoxymethyl-acrylamide, N-n-butyl-acrylamide,N-2-cyanoethyl-acrylamide, N-cyanomethyl-acrylamide,N-cyanomethyl-N-methyl-acrylamide, N,N-diallyl-acrylamide,N,N-diisopropyl-acrylamide, N-ethyl-N-methyl-acrylamide,N-ethyl-N-propyl-acrylamide, N-2-glycolic acid-acrylamide, N-2-glycolicacid methyl ester-acrylamide, N-2-hydroxyethyl-acrylamide,N-2-hydroxyethyl-N-methyl-acrylamide, N-hydroxymethyl-acrylamide,N-hydroxymethyl-N-methyl-acrylamide, N-2-methoxyethyl-acrylamide,N-methoxymethyl-acrylamide, N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)methyl-acrylamide,N-tri(hydroxymethyl)methyl-N-methyl-acrylamide,N-3-(trimethylammonium)propyl-acrylamide hydrochloride,N-3-(trimethylammonium)propyl-N-methyl-acrylamide hydrochloride,N-acetamido-methacrylamide, N-acetyl-methacrylamide,N-allyl-methacrylamide, N-2-aminoethyl-methacrylamide hydrochloride,N-3-aminopropyl-methacrylamide hydrochloride,N-butoxymethyl-methacrylamide, N-n-butyl-methacrylamide,N-tert-butyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N-cyanomethyl-methacrylamide, N-cyanomethyl-N-methyl-methacrylamide,N,N-diethyl-methacrylamide, N,N-dimethyl-methacrylamide, N-2-glycolicacid-methacrylamide, N-2-hydroxyethyl-methacrylamide,N-hydroxymethyl-methacrylamide, N-hydroxymethyl-N-methyl-methacrylamide,N-iso-propyl-methacrylamide, N-2-methoxyethyl-methacrylamide,N-methoxymethyl-methacrylamide, N-methyl-methacrylamide,N-tri(hydroxymethyl)methyl-methacrylamide,N-3-(trimethylammonium)propyl-methacrylamide hydrochloride, or a mixturethereof.

In other embodiments, in each of the preceding embodiments for M₂, eachM₁, or each monomer subtype of type M₁ if x>1, is independentlyN-vinylformamide, N-vinylacetamide or N-methyl-N-vinylacetamide or,alternatively, each M₁, or each monomer subtype of type M₁ if x>1, isindependently N-vinylformamide or N-methyl-N-vinylacetamide.

In other embodiments, the polymer of the invention is a copolymer thatis poly(N-vinylformamide-co-N-methyl-acrylamide);poly(N-vinylformamide-co-N,N-diethyl-acrylamide);poly(N-vinylformamide-co-N-methoxymethyl-acrylamide);poly(N-vinylformamide-co-N-methoxy-acrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-acrylamide);poly(N-vinylformamide-co-N-methyl-methacrylamide);poly(N-vinylformamide-co-N,N-dimethyl-methacrylamide);poly(N-vinylformamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-vinylformamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-vinylformamide-co-2-vinylene carbonate);poly(N-vinylformamide-co-vinyl acetate-co-2-vinylene carbonate);poly(N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-vinylacetamide-co-N-methoxy-acrylamide);poly(N-vinylacetamide-co-N-2-hydroxyethyl-acrylamide);poly(N-vinylacetamide-co-methacrylamide);poly(N-vinylacetamide-co-N-methyl-methacrylamide);poly(N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylacetamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-vinylacetamide-co-2-vinylene carbonate);poly(N-vinylacetamide-co-vinyl acetate-co-2-vinylene carbonate);poly(N-methyl-N-vinylacetamide-co-N-methyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-diethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxy-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-dimethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-methyl-N-vinylacetamide-co-2-vinylene carbonate);poly(N-methyl-N-vinylacetamide-co-vinyl acetate-co-2-vinylenecarbonate); or salts thereof.

In other embodiments, the polymer of the invention is a copolymer thatis poly(N-vinylformamide-co-N-methoxymethyl-acrylamide);poly(N-vinylformamide-co-N-methoxy-acrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-acrylamide);poly(N-vinylformamide-co-N-methyl-methacrylamide);poly(N-vinylformamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-vinylformamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-vinylformamide-co-2-vinylene carbonate);poly(N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-vinylacetamide-co-N-methoxy-acrylamide);poly(N-vinylacetamide-co-N-2-hydroxyethyl-acrylamide);poly(N-vinylacetamide-co-N-methyl-methacrylamide);poly(N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylacetamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-vinylacetamide-co-2-vinylene carbonate);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxy-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-methyl-N-vinylacetamide-co-2-vinylene carbonate); or saltsthereof.

In other embodiments, the polymer of the invention is a copolymer thatis poly(N-vinylformamide-co-N-methyl-acrylamide);poly(N-vinylformamide-co-N,N-diethyl-acrylamide);poly(N-vinylformamide-co-N-methoxymethyl-acrylamide);poly(N-vinylformamide-co-N-methoxy-acrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-acrylamide);poly(N-vinylformamide-co-N-methyl-methacrylamide);poly(N-vinylformamide-co-N,N-dimethyl-methacrylamide);poly(N-vinylformamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-vinylformamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-vinylformamide-co-2-vinylene carbonate);poly(N-vinylformamide-co-vinyl acetate-co-2-vinylene carbonate);poly(N-methyl-N-vinylacetamide-co-N-methyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-diethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxy-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-dimethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-methyl-N-vinylacetamide-co-2-vinylene carbonate);poly(N-methyl-N-vinylacetamide-co-vinyl acetate-co-2-vinylenecarbonate); or salts thereof.

In other embodiments, the polymer of the invention is a copolymer thatis poly(N-vinylformamide-co-N-methoxymethyl-acrylamide);poly(N-vinylformamide-co-N-methoxy-acrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-acrylamide);poly(N-vinylformamide-co-N-methyl-methacrylamide);poly(N-vinylformamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-vinylformamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-vinylformamide-co-2-vinylene carbonate);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxy-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-methyl-N-vinylacetamide-co-2-vinylene carbonate); or saltsthereof.

As used herein, “—(C₁-C₁₀ alkyl)” means a saturated straight chain orbranched non-cyclic hydrocarbon having from 1 to 10 carbon atoms.Representative saturated straight chain —(C₁-C₁₀ alkyls) include-methyl, -ethyl, —N-propyl, —N-butyl, —N-pentyl, —N-hexyl, —N-heptyl,—N-octyl, —N-nonyl, and —N-decyl. Representative saturated branched—(C₁-C₁₀ alkyls) include -isopropyl, -sec-butyl, -iso-butyl,-tert-butyl, -isopentyl, -2-methylbutyl, -3-methylbutyl,-2,2-dimethylbutyl, -2,3-dimethylbutyl, -2-methylpentyl,-3-methylpentyl, -4-methylpentyl, -2-methylhexyl, -3-methylhexyl,-4-methylhexyl, -5-methylhexyl, -2,3-dimethylbutyl, -2,3-dimethylpentyl,-2,4-dimethylpentyl, -2,3-dimethylhexyl, -2,4-dimethylhexyl,-2,5-dimethylhexyl, -2,2-dimethylpentyl, -2,2-dimethylhexyl,-3,3-dimethylpentyl, -3,3-dimethylhexyl, -4,4-dimethylhexyl,-2-ethylpentyl, -3-ethylpentyl, -2-ethylhexyl, -3-ethylhexyl,-4-ethylhexyl, -2-methyl-2-ethylpentyl, -2-methyl-3-ethylpentyl,-2-methyl-4-ethylpentyl, -2-methyl-2-ethylhexyl, -2-methyl-3-ethylhexyl,-2-methyl-4-ethylhexyl, -2,2-diethylpentyl, -3,3-diethylhexyl,-2,2-diethylhexyl, -3,3-diethylhexyl and the like.

As used herein, “—(C₁-C₄ alkyl)” means a saturated straight chain orbranched non-cyclic hydrocarbon having from 1 to 4 carbon atoms.Representative saturated straight chain —(C₁-C₄ alkyls) include -methyl,-ethyl, —N-propyl, and —N-butyl. Representative saturated branched—(C₁-C₄ alkyls) include -isopropyl, -sec-butyl, -iso-butyl, and-tert-butyl.

As used herein, “—(C₁-C₁₀ heteroalkyl)” broadly refers to a —(C₁-C₁₀alkyl) where up to three carbon atoms are replaced by and/or substitutedwith a heteroatom. Thus, a —(C₁-C₁₀ heteroalkyl) possesses in-chain,pendant and/or terminal functionality, as understood by those personsskilled in the relevant art. As examples of in-chain functionality canbe mentioned a carbonyl group or groups (which is/are, of course,included in the carbon count), heteroatom or heteroatoms (such as atleast one oxygen, sulfur, nitrogen, phosphorous or silicon) in thechain, esters, amides, urethanes and their thio-derivatives, i.e., whereat least one oxygen atom is replaced by a sulfur atom. As examples ofpendant and/or terminal functionality can be mentioned groups such ashydroxyl, amino, cyano, aldehyde, carboxyl, esters of carboxyl, thio,thiocarboxyl, esters of thiocarboxyl, amido, and halogen. Thus,exemplary —(C₁-C₁₀ heteroalkyl) groups include methoxy; ethoxy; propoxy;butoxymethyl; dimethoxybutyl; dimethoxyethyl; 3-(trimethylammoniumchloride)-propyl; acetyl; cyanomethyl; cyanoethyl; 2-methoxyethyl;glycolic acid; glycolic acid esters, such as methyl ester;hydroxymethyl; methoxymethyl; methoxypropyl;2,2,2-trichloro-1-hydroxyethyl; tri(hydroxymethyl)-methyl;pentafluoroethyl; 3-iodopropyl and the like.

As used herein, “—(C₃-C₈ cycloalkyl)” means a saturated cyclichydrocarbon having from 3 to 8 carbon atoms. Representative —(C₃-C₈cycloalkyls) include -cyclopropyl, -cyclobutyl, -cyclopentyl,-cyclohexyl, -cycloheptyl and -cyclooctyl.

As used herein, “-(3- to 8-membered heterocycloalkyl)” broadly refers toan aliphatic heterocycle ring of 3 to 8 members where at least onecarbon atom is replaced with a heteroatom that is independentlynitrogen, oxygen or sulfur. A -(3-membered heterocycloalkyl)'s ring canhave one heteroatom. A -(4- to 5-membered heterocycloalkyl)'s ring canhave one or two heteroatoms. A -(6- to 8-membered heterocycloalkyl)'sring can have one, two or three heteroatoms. Representative -(3- to8-membered heterocycloalkyl)s include epoxide, 1,4-dioxane,tetrahydrofuran, morpholine, 1H-azepine, piperidine, piperazine,tetrahydrothiophene, thiomorpholine and the like.

As used herein, “aryl” refers phenyl, naphthyl, anthryl and phenanthryl.

As used herein, “-(5- to 10-membered heteroaryl)” means an aromaticheterocycle ring of 5 to 10 members, including both mono- and bicyclicring systems, where at least one carbon atom of one or both of the ringsis replaced with a heteroatom that is independently nitrogen, oxygen, orsulfur. One or both of the -(5- to 10-membered heteroaryl)'s ringscontain at least one carbon atom. Representative (5- to 10-memberedheteroaryl)s include pyridyl, furyl, benzofuranyl, thiophenyl,benzothiophenyl, quinolinyl, pyrrolyl, indolyl, oxazolyl, benzoxazolyl,imidazolyl, benzimidazolyl, thiazolyl, benzothiazolyl, isoxazolyl,pyrazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl,cinnolinyl, phthalazinyl and quinazolinyl.

As used herein, a “compound term,” e.g., —(C₃-C₈ cycloalkyl)(C₁-C₁₀heteroalkyl), broadly refers to a monovalent first group, here C₃-C₈cycloalkyl, in which the valency is derived by abstraction of a hydrogenfrom a carbon atom or heteroatom, where the first group is furthersubstituted with one or more second group(s), here a C₁-C₁₀ heteroalkylgroup(s), e.g., 3-chloromethylcyclohexyl or3,4-di(chloromethyl)cyclohexyl. As a further illustration, a compoundterm such as —(C₁-C₁₀ alkyl)(aryl) refers to a first group, here C₁-C₁₀alkyl, which is further substituted with one or more second group(s),here an aryl group(s). Illustrative —(C₁-C₁₀ alkyl)(aryl) groups arebenzyl and 2,2-diphenyl ethyl.

As used herein, a “salt” of a polymer refers to a polymer having atleast one anionic charge, cationic charge, or both, e.g., an amphotericpolymer, where each charge has associated with it a counterion.“Counterion” refers to an ion that balances the polymer's anionic orcationic charge. Exemplary counterions for a polymer comprising acationic charge include chloride, bromide, iodide, hydroxide, alkoxide,carbonate, bicarbonate, oxide, formate, sulfate, benzene sulfonate,p-toluenesulfonate, p-bromobenzenesulfonate, methanesulfonate,trifluoromethanesulfonate, phosphate, perchlorate, tetrafluoroborate,tetraphenylboride, nitrate and anions of aromatic or aliphaticcarboxylic acids. Exemplary counterions for a polymer comprising ananionic charge include NH₄ ⁺, tetraalkyl ammonium, quaternaryphosphonium, such as a tetraalkyl phosphonium halide, triethyl amine,trimethyl amine and 2-amino-2-(hydroxymethyl)-1,3-propanediol (“TRIS”),and the cations of Li, Na, K, Rb, Cs and Ag. In certain embodiments, thecounterions include chloride, p-toluenesulfonate, lithium, sodium andpotassium.

In one embodiment, a polymer of the invention is a random copolymer. Inanother embodiment, a polymer of the invention is a substantially randomcopolymer, i.e., the polymer of the invention has more random copolymerunits that alternating copolymer units. In another embodiment, a polymerof the invention is a nearly random copolymer, i.e., when thecopolymerization by which the polymer of the invention is formed isstopped at a conversion of less than 50 mol % of the total monomercontent, the polymer of the invention has more random copolymer unitsthat alternating copolymer units.

In one embodiment, a polymer of the invention is water soluble,water-swellable, or both, at atmospheric pressure, a concentration offrom about 0.01 to about 1 wt. %, and from about 20° C. to about 70° C.in water. In another embodiment, a polymer of the invention is watersoluble, water-swellable, or both, at about 25° C. in water. Forpurposes of this invention, water-swellable polymers of the inventionare generally those that swell in water but are not completely solublebecause they have a very slow dissolution rate, e.g., polymers that aresubstantially uncrosslinked but have an extremely high weight-averagemolecular weight (“Mw”); or those unable to dissolve completely in waterbecause they have been crosslinked to a certain low degree, for example,when a polymer of the invention comprises an amount of a crosslinking orbranching agent. In one embodiment, a polymer of the invention is ableto flow into or out of a capillary either with or without the assistanceof pressure or vacuum. In another embodiment, a polymer of the inventionis uncrosslinked. In another embodiment, a polymer of the invention issubstantially uncrosslinked.

The Mw of a polymer of the invention can vary widely. In one embodiment,the Mw of a polymer of the invention is at least about 150,000 Daltons.In another embodiment, the Mw of a polymer of the invention is at leastabout 200,000 Da. In another embodiment, the Mw of a polymer of theinvention is at least about 500,000 Da. In another embodiment, the Mw ofa polymer of the invention is at least about 1 MDaltons. In anotherembodiment, the Mw of a polymer of the invention is at least about 2MDa. In another embodiment, the Mw of a polymer of the invention is fromabout 150,000 Da to about 20 MDa. In another embodiment, the Mw of apolymer of the invention is from about 500,000 Da to about 10 MDa. Inanother embodiment, the Mw of a polymer of the invention is from about 1MDa to about 20 MDa. In another embodiment, the Mw of a polymer of theinvention is from about 1 MDa to about 5 MDa. In another embodiment, theMw of a polymer of the invention is from about 500,000 Da to about 5MDa.

The molecular weight of a polymer of the invention can be determinedusing conventional methods. The conventional method of gel permeationchromatography (“GPC”), also known as size exclusion chromatography orSEC, is a way for determining the molecular weight of polymers andcopolymers. The fundamentals of applying a multi-angle laser lightscattering detector to GPC instrumentation (“GPC-MALLS”) for theabsolute characterization of polymers, such as the determination oftheir number-average and weight-average molecular weights, areconventional, e.g, see Wyatt, Analytica Chimica Acta 272:1-40 (1993).For example, GPC-MALLS has been used to determine, inter alia, the Mw ofseveral water-soluble polymers and copolymers having molecular weightsof from below 50,000 Da to over 1 MDa. Nagy, Proc. Int'l. GPC Symposium,Orlando, Fla., June 1994 95-0315:71-95 (1994). Moreover, the use of GPCand, in particular, GPC-MALLS, for molecular weight determinations iswell-recognized in the art. For example, the GPC molecular weightresults obtained for identical polymer samples using several differentadvanced on-line detection systems, including GPC-MALLS comparefavorably. S. Yau, Chemtracts—Macromolecular Chemistry 1:1-36 (1990).Therefore, GPC-MALLS is a conventional way for determining thenumber-average (“Mn”) and weight-average molecular weights of a polymerof the invention.

4.2. Method for Making Polymers of the Invention

Many methods of making polymers are known in the art and can be used toprepare the polymer of the invention. Such polymerizations can beconducted in bulk, solution, suspension, emulsion or microemulsion, anda wide variety of polymerization initiators can be used. For example,several such methods are summarized in the following chapter: C. A.Costello et al., Copolymers in Kirk-Othmer Encyc. of Chem. Technol. Vol.7, 349-381 (4^(th) ed. 1993).

Thus, a second embodiment of the invention relates to a method formaking a polymer of the invention, comprising the step of polymerizingan M₁, optionally in the presence of an M₂, to provide a polymer of theinvention. It is to be understood that a polymer of the invention can bea homopolymer or a copolymer. The polymerization can be initiated by atleast one free-radical, anionic and/or cationic initiator. In anotherembodiment, the polymerization is initiated by at least one free-radicalinitiator. The free-radical initiator can be dissociated thermally orphotolytically in initiating the polymerization. In another embodiment,the present invention relates to the polymer of the invention product ofany of the methods herein for making it.

A polymerization reaction can be carried out by conventional methods,e.g., by free-radical initiation of monomer(s), thereby forming thepolymer of the invention. Without being bound by a particular theory, aproposed mechanism for polymerization yielding an exemplary polymer ofthe invention is shown in the following Scheme 1. Free-radicals formed,for example, by the thermal or photolytic decomposition of afree-radical initiator at the start of polymerization, can initiate thepolymerization of monomer (I) to form polymer (P).

In another embodiment of a method for making a polymer of the invention,M₁ is N-vinylformamide (“VF”) (III), N-vinylacetamide (IV),N-methyl-N-vinylacetamide (“MVA”) (V), or a mixture thereof, each ofthese monomers being illustrated in the following Scheme 2.

In another embodiment, the comonomers for making a polymer of theinvention can be water-soluble.

In another embodiment, the free-radical initiator(s) for making thepolymer of the invention are thermally or photolytically dissociatedinitiators selected from azo compounds, diazo compounds, organicperoxides, organic hydroperoxides, organic persulfates, organichydropersulfates, inorganic peroxides, inorganic persulfates,peroxide-redox systems, carbon-carbon initiators, photoinitiators, or amixture thereof.

Many types of free-radical initiators can be used, e.g., azo and diazocompounds, such as azo-bis-isobutyronitrile (“AIBN”), organic peroxides,hydroperoxides, persulfates and hydropersulfates, such as benzoylperoxide, inorganic peroxides and persulfates, such as theperoxide-redox systems, carbon-carbon initiators, such ashexasubstituted ethanes, and photoinitiators; numerous examples areknown in the art. See Sanchez et al., Initiators (Free-Radical) inKirk-Othmer Encyc. of Chem. Technol. Vol. 14, 431-460 (4^(th) ed. 1993).Anionic initiators are known in the art and include aromatic radicalanions, such as sodium naphthalene; alkyl lithium compounds, such ast-butyl lithium; fluorenyl carbanions; 1,1-diphenylmethylcarbanions;cumyl potassium; and those described by Quirk et al., Initiators(Anionic) in Kirk-Othmer Encyc. of Chem. Technol. Vol. 14, 461-476(4^(th) ed. 1993). Cationic initiators are also known in the art andinclude protic acids, cation donor (initiator)/Friedel-Crafts acid(coinitiator) systems, stable cation salts, and those described byFaust, Initiators (Cationic) in Kirk-Othmer Encyc. of Chem. Technol.Vol. 14, 476-482 (4^(th) ed. 1995). The free-radical, anionic orcationic initiator can undergo decomposition by any known means, e.g.,thermally or photolytically, when this is required to initiatepolymerization.

In another embodiment, the polymer of the invention can be preparedusing free-radical polymerization in aqueous solution.

In another embodiment, the polymer of the invention can be preparedusing aqueous solution free-radical polymerization with at least one awater-soluble azo initiator.

Of course, other ways for initiating polymerization known in the art canalso be used to make the polymer of the invention. For example, exposinga combination of M₁ and, optionally, any other monomer(s) to an electronbeam, ultraviolet radiation, usually in the presence of aphotoinitiator, and high energy ionizing radiation sources, such asγ-radiation from a ⁶⁰Co or ¹³⁷Cs source, α-particles, β-particles, fastneutrons and x-rays, can cause the generation of free-radicals and/orions that, in turN, initiate polymerization. Sanchez et al., Initiators(Free-Radical)” at 454-457; Sheppard et al., Initiators in Kirk-OthmerEncyc. of Chem. Technol. Vol. 13, 367-370 (3^(rd) ed. 1981).

The Mw of the polymer of the invention can vary widely. Those skilled inthe art will recognize that polymer of the invention having a particularMw can be obtained using conventional methods, e.g., using a chaintransfer agent, such as N-butanol or isopropanol, and/or varying theamount of chain transfer agent present. The Mw can be increased bydecreasing the initiator concentration relative to the starting monomerconcentration and/or decreasing the amount of chain transfer agentpresent, or even eliminating the chain transfer agent entirely.

The polymer of the invention can be prepared using the method of inverseemulsion polymerization (“IEP”). Many aspects of the IEP method havebeen described in detail by, e.g., “Inverse Emulsion (Microemulsion)Polymerization,” Chapter 4 in Radical Polymerization in DisperseSystems, Barton et al., Ellis Horwood, New York, 1994, pp. 187-215;Candau et al., J. Polym. Sci., Polym. Chem. Ed., 23:193-214 (1985); andPross et al., Polym. Int'l., 45:22-26 (1998). IEP is sometimes referredto as inverse microsuspension polymerization (Pross, p. 22.) or asinverse microemulsion polymerization (Barton, Id.).

Any oil can be used to form the inverse emulsion. To make polymer of theinvention from an N-vinylamide-type monomer(s), the N-vinylamide shouldbe present in the water phase. Without being bound by a particulartheory, because N-vinylamides are partially soluble in the oils commonlyused in the art as the oil phase for IEP, its oil-solubility is thoughtto limit the maximum molecular weight of the polymer produced when usingsuch oils. Thus, when polymers of the invention are to be made, it isdesirable, but not required, that their monomer(s) be substantiallyinsoluble in the oil selected.

For the purpose of selecting an appropriate monomer/oil combination,“oil insoluble” is defined as follows. At a temperature of 20° C.throughout, 1 mL of the selected monomer or monomer mixture is placedinto 6 mL of the selected oil(s) and vortex mixed for 1 minute. Themixing is stopped and the liquid is allowed to stand for 10 minutes. Themonomer(s) is oil insoluble if phase separation, e.g., translucency,cloudiness and/or separate layers, can be observed with the unaided eyeafter the 10 minute period. Conversely, the monomer(s) is not oilinsoluble if no phase separation, i.e., a clear solution, is observedafter the 10 minute period.

For example, by this test N-vinylamides were determined to be not oilinsoluble in each of acetonitrile, acetone, methanol, 1-decanol, ethylether, hexane, decane, petroleum ether (normal boiling range 35-60° C.),and petroleum special (normal boiling range 180-220° C.). However,N-vinylamides were determined to be oil insoluble by this test in, e.g.,aliphatic hydrocarbons comprising at least about 15 carbon atoms. Inaddition, N-vinylamides were determined to be oil insoluble by this testin, e.g., aliphatic hydrocarbons with a normal boiling point at or aboveabout 270° C. Exemplary hydrocarbons that are can be used as oils forforming the N-vinylamide polymers and copolymers of the invention by IEPfrom N-vinylamides include pentadecane, hexadecane, heptadecane, whitelight mineral or paraffin oils, white heavy mineral or paraffin oils,and mineral or paraffin oils for Nujol preparations.

N-vinylamides are also oil insoluble using the above test in, e.g.,silicone oils, at least partially fluorinated hydrocarbons and liquidperfluoropolyethers (“PFPE”), also known as perfluoropolyalkylethers(“PFPAE”).

Exemplary silicones that are conventional and can be used as oils forforming the polymer of the invention by IEP from includepoly(dimethylsiloxane)-based oils such as DC200, DC510, DC550 and DC710,each of which can be available in various viscosity grades (e.g., from10 cSt to 12,500 cSt for DC200) from Dow Corning andpoly(methylphenylsiloxane)-based oils such as AR200, also from DowCorning.

Exemplary at least partially fluorinated hydrocarbon liquids that areconventional and can be used as oils for forming the polymer of theinvention by IEP include the FLUORINERT series available from 3M, e.g.,FC-40, FC-43, FC-70, FC-72, FC-77, FC-84, FC-87, FC-3283, FC-5312 andFC-5320

Exemplary liquid PFPEs that are conventional and can be used as oils forforming the polymer of the invention by IEP include the DEMNUIM seriesavailable from Daikin Industries, Ltd., e.g., S-20, S-65, S-100 andS-200, the KRYTOX series available from DuPont, e.g., GPL100, GPL101,GPL102, GPL103, GPL104, GPL105, GPL106, GPL107, 143AB, 143AC andVPF1525, and the FOMBLIN Y, Z and M series available from AusimontMontedison Group, e.g., Y04, Y06, Y25, Y-L VAC 25/6, YR, YR1500, YR1800,Z03, Z15, Z25, Z60, M03, M15, M30 and M60. As disclosed by, e.g.,Hamada, Phys. Chem. Chem. Phys., 2:115-122 (2000), the DEMNUIM-typePFPEs have the formula F—[CF₂CF₂CF₂O]_(n)—H, the KRYTOX-type PFPEs havethe formula F—[CF(CF₃)CF₂O]_(l)—H, and the FOMBLIN-Z-type PFPEs have theformula F—[(CF₂CF₂O)₂—(CF₂O)]_(m)—H, where n, l and m are varied togive, e.g., different chain lengths and viscosities.

In one embodiment, oils for the IEP of N-vinylamides to obtain polymerof the invention include aliphatic hydrocarbons comprising at leastabout 15 carbon atoms, aliphatic hydrocarbons having a normal boilingpoint at or above about 270° C., silicone oils, at least partiallyfluorinated hydrocarbons, liquid perfluoropolyethers, or a mixturethereof. In another embodiment, oils for the IEP of N-vinylamides toobtain polymer of the invention include pentadecane, hexadecane,heptadecane, white light mineral oils, white heavy mineral oils, andmineral oils for Nujol preparations. In another embodiment, the oil usedfor the IEP of N-vinylamides to obtain the polymer of the invention is amineral oil for Nujol preparations.

At least one surfactant can be used to form the inverse emulsion. Whenan additional surfactant is present, the additional surfactant issometimes known as a cosurfactant. It is conventional to characterize asurfactant by its hydrophilic lipophilic balance (“HLB”), a measure ofthe relative simultaneous attraction of the surfactant for water or oil.On the HLB scale ranging from 1 to 40, relatively lipophilic surfactantshave a low numerical value while relatively hydrophilic surfactants havea high numerical value.

A wide variety of surfactants are known to be available, for example,many are listed with HLB values in McCutcheon's Emulsifiers &Detergents, North American Ed., Manufacturing Confectioner Pub. Co.,Glen Rock, N.J., 1988, pp. 1-217. The surfactant can be nonionic or havean anionic charge, cationic charge, or both, e.g., an amphotericsurfactant, where each charge has associated with it a counterion;numerous examples of each are known in the art. See Lyn N, Jr. et al.,Surfactants in Kirk-Othmer Encyc. of Chem. Technol. Vol. 23, 483-541(4^(th) ed. 1997).

Nonionic surfactants are known in the art and include polyoxyethylenesurfactants, e.g., alcohol ethoxylates and alkylphenol ethoxylates;carboxylic acid esters, e.g., glycerol esters and polyoxyethyleneesters; anhydrosorbitol esters, e.g., mono-, di- and tri-esters ofsorbitan and fatty acids; polyalkylene oxide block copolymers; andpoly(oxyethylene-co-oxypropylene) nonionic surfactants. Id., pp.506-523.

Anionic surfactants are known in the art and include carboxylates, e.g.,soaps, polyalkoxycarboxylates and N-acylsarcosinates; sulfonates, e.g.,alkylbenzene sulfonates, naphthalene sulfonates and petroleumsulfonates; sulfates, e.g., alcohol sulfates and ethoxylated andsulfated alcohols; and phosphates, e.g., phosphate esters. Id., pp.491-505.

Cationic surfactants are known in the art and include amines, e.g.,aliphatic mono-, di- and polyamines derived from fatty and rosin acids;and quaternary ammonium salts, e.g., dialkyldimethyl and alkyltrimethylammonium salts, alkylbenzyldimethyl ammonium chlorides, andalkylpyridinium halides. Id., pp. 524-530. Amphoteric surfactants areknown in the art and include alkylbetaines, amidopropylbetaines andimidazolinium derivatives. Id., pp. 530-532.

Considerations typically taken into account in selecting a surfactant orsurfactant blend to form an inverse emulsion are conventional and aresummarized in, e.g., Griffin, Emulsions in Kirk-Othmer Encyc. of Chem.Technol. Vol. 8, 909-919 (3^(rd) ed. 1979). Furthermore, it isrecognized that some monomers, e.g., acrylamide, can sometimes act as aco-surfactant. Candau, p. 204; Barton, p. 191. In such cases, theoverall HLB value of the emulsification system can differ from the HLBof the selected surfactant or surfactant blend. Barton, p. 191.Moreover, those in the art recognize that particular characteristics ofthe inverse emulsion must be taken into account when selecting asurfactant. For example, when a fluorinated oil is used, it is desirableto also select an at least partially fluorinated surfactant. Taking suchconventional factors into consideration, one skilled in the art is ableto select a wide variety of surfactants, used individually or incombination, for the IEP of water-soluble monomers to form highmolecular weight polymers and, particularly, to form polymer of theinvention from N-vinylamides by IEP.

In one embodiment, surfactants for the IEP of N-vinylamides to thepolymer of the invention have an HLB of about 7 or less. In anotherembodiment, the surfactant HLB is about 6 or less. In anotherembodiment, the surfactant HLB is from about 3 to about 6. In anotherembodiment, surfactants for the IEP of N-vinylamides to the polymer ofthe invention have an HLB of from about 4 to about 6. In anotherembodiment, surfactants include SPAN-80 from Fluka, sorbitan monooleatethought to have the following structure:

with a molecular weight of about 429 Da and an HLB of about 4.3;TETRONIC 1301 from BASF, an amine-based block copolymer nonionicsurfactant thought to have the following structure:

with a molecular weight of about 6,800 Da and an HLB of about 2.0; or amixture thereof.

A sufficient amount of the surfactant is used such that a stableemulsion or microemulsion is formed; routine experimentation by oneskilled in the art can be used to determine that amount. To obtain,after polymerization, a microemulsion of high polymer content, the ratio(by weight) of aqueous phase to oil phase is usually chosen to be ashigh as possible. This ratio can range, for example, from about 1:10 toabout 4:1. In another embodiment, the ratio can range from about 1:2 toabout 3:1. In another embodiment, the quantity of solid polymer productis greater than about 10 wt. % of the total emulsion weight.

Many types of initiators discussed above can are be used for inverseemulsion polymerizations, e.g., free-radical initiators such as the azocompounds, organic peroxides and persulfates, inorganic peroxides andpersulfates, and carbon-carbon initiators, as well as photoinitiatorssuch as those described in McGinniss, Radiation Curing in Kirk-OthmerEncyc. of Chem. Technol. Vol. 20, 848-850 (4^(th) ed. 1996).Polymerization can, of course, also be effected by high energy ionizingradiation sources.

In one embodiment, inverse emulsion polymerization initiators includethe azo compounds, either the oil-soluble types such as AIBN or thewater-soluble types such as azobutyroamidine, oil-soluble peroxides andpersulfates, such as dibenzoyl peroxide, water soluble peroxides andpersulfates, such as ammonium persulfate and potassium persulfate, redoxinitiating systems, which include the peroxy-redox types and, e.g.,K₂S₂O₈/Na₂S₂O₅ or ferrous ammonium sulfate/ammonium persulfate, andphotoinitiators, such as Michler's ketone, i.e.,4,4′-bis-(dimethylamino)benzophenone, and IRGACURE-1700 andDAROCURE-1173 from Ciba-Geigy, believed to be (25%bis-(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide+75%2-hydroxy-2-methyl-1-phenyl-propan-1-one) and2-hydroxy-2-methyl-1-phenyl-propan-1-one, respectively. In anotherembodiment, initiators for the IEP of N-vinylamides to the N-vinylamidepolymers and copolymers of the invention include oil-soluble azocompounds, water soluble peroxides and persulfates, redox initiatingsystems, photoinitiators, or a mixture thereof. In another embodiment,the initiator used for the IEP of N-vinylamides to the polymer of theinvention is AIBN, ammonium persulfate, potassium persulfate, Michler'sketone, 2-hydroxy-2-methyl-1-phenyl-propan-1-one,bis-(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentylphosphine oxide, or amixture thereof.

The inverse emulsion and/or its aqueous phase can also contain suchother additives if desired. These include chain transfer agents, pHadjusters, co-initiators, sensitizers, charge-transfer complexes ordonor-acceptor complexes when photoinitiation is used, chelating agentsfor removing polymerization inhibitors, and other conventional additivesused in their usual proportions. Polymerization in the inverse emulsionor microemulsion can be carried out by any manner known to those skilledin the art, e.g., as generally described in Griffin, pp. 919-923; U.S.Pat. No. 5,530,069 to Neff et al., at col. 3, lines 39-65 and col. 5,line 29 to col. 6, line 44; and in the references cited therein.

In another embodiment, the present invention relates to the polymer ofthe invention, methods for making the same, and polymer of the inventionmade by the methods disclosed herein.

4.3. Compositions of the Invention

A third embodiment of the invention relates to a composition comprisinga polymer of the invention (e.g., see Section 4.1) and a buffer. Thecomposition is useful as an electrophoresis separation medium. In someembodiments, the composition further comprises a second polymer or asalt thereof (described in further detail below). In another embodiment,the composition further comprises a denaturant. In the compositions, thepolymer of the invention comprises one or more monomers of type M₁ andoptionally one or more monomers of type M₂, such that:

(a) each monomer in the polymer is of type M₁ or M₂;

(b) x is an integer ranging from 1 to 5 and represents the number ofmonomer subtypes of type M₁ that are present in the polymer;

(c) y is an integer ranging from 0 to 5 and represents the number ofmonomer subtypes of type M₂ that are present in the polymer;

(d) each monomer subtype of type M₁ in the polymer independently has theformula (I):

-   -   where each A₁ is independently ═O, ═S or ═NX₁;    -   each of R₁, R₂, R₃ and R₄ is independently —H, —(C₁-C₁₀ alkyl),        —(C₃-C₈ cycloalkyl), -(aryl), -(5- to 10-membered heteroaryl),        —(C₁-C₁₀ alkyl)(aryl) or -(aryl)(C₁-C₁₀ alkyl);    -   each R₅ is independently —(H), —(C₁-C₁₀ alkyl), —(C₁-C₁₀        heteroalkyl), —(C₃-C₈ cycloalkyl), -(3- to 8-membered        heterocycloalkyl), -(aryl), -(5- to 10-membered heteroaryl),        —(C₁-C₁₀ alkyl)(C₃-C₈ cycloalkyl), —(C₃-C₈ cycloalkyl)(C₁-C₁₀        alkyl), —(C₁-C₁₀ heteroalkyl)(C₃-C₈ cycloalkyl), —(C₃-C₈        cycloalkyl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀ alkyl)(3- to        8-membered heterocycloalkyl), -(3- to 8-membered        heterocycloalkyl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(3- to        8-membered heterocycloalkyl), -(3- to 8-membered        heterocycloalkyl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀ alkyl)(aryl),        -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(aryl),        -(aryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀ alkyl)(5- to 10-membered        heteroaryl), -(5- to 10-membered heteroaryl)(C₁-C₁₀ alkyl),        —(C₁-C₁₀ heteroalkyl)(5- to 10-membered heteroaryl), -(5- to        10-membered heteroaryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₄        alkyl)_(p)NH₂, —(C₁-C₄ alkyl)_(p)CONH₂, —(C₁-C₄ alkyl)NHCONH₂,        —(C₁-C₄ alkyl)NHCOH or —(C₁-C₄ alkyl)_(p)NHCOCH₃, where each p        is 0 or 1; and    -   each X₁ is independently —H, —(C₁-C₁₀ alkyl), —(C₃-C₈        cycloalkyl), -(aryl), -(5- to 10-membered heteroaryl), —(C₁-C₁₀        alkyl)(aryl), -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₄ alkyl)_(p)NH₂,        —(C₁-C₄ alkyl)_(p)CONH₂, —(C₁-C₄ alkyl)NHCONH₂, —(C₁-C₄        alkyl)_(p)NHCOH or —(C₁-C₄ alkyl)_(p)NHCOCH₃, where each p is 0        or 1; and        (e) when y is not zero, each monomer subtype of type M₂ in the        polymer is independently:    -   1-vinyl-pyrrolidine-2,5-dione;    -   3-vinyl-oxazolidin-2-one;    -   1-vinyl-imidazolidin-2-one;    -   4-vinyl-morpholin-3,5-dione;    -   4-vinyl-morpholin-3-one;    -   4-vinyl-morpholine;    -   2-vinyl-1,3-dioxolane;    -   2-vinylene carbonate;    -   methoxyethylene;    -   vinyl acetate;    -   vinyl alcohol;    -   a monomer of formula (II):

-   -   -   where each A₂ is independently ═O, ═S or ═NX₂;        -   each of R₆, R₇, R₈ and R₉ is independently —H, —(C₁-C₁₀            alkyl), —(C₃-C₈ cycloalkyl), -(aryl), -(5- to 10-membered            heteroaryl), —(C₁-C₁₀ alkyl)(aryl) or -(aryl)(C₁-C₁₀ alkyl);        -   each R₁₀ is independently —H, —OH, —(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl), —(C₃-C₈ cycloalkyl), -(3- to 8-membered            heterocycloalkyl), -(aryl), -(5- to 10-membered heteroaryl),            —(C₁-C₁₀ alkyl)(C₃-C₈ cycloalkyl), —(C₃-C₈            cycloalkyl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(C₃-C₈            cycloalkyl), —(C₄-C₈ cycloalkyl)(C₁-C₁₀ heteroalkyl),            —(C₁-C₁₀ alkyl)(3- to 8-membered heterocycloalkyl), -(3- to            8-membered heterocycloalkyl)(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl)(3- to 8-membered heterocycloalkyl), -(3- to            8-membered heterocycloalkyl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀            alkyl)(aryl), -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl)(aryl), -(aryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₁₀            alkyl)(5- to 10-membered heteroaryl), -(5- to 10-membered            heteroaryl)(C₁-C₁₀ alkyl), —(C₁-C₁₀ heteroalkyl)(5- to            10-membered heteroaryl), -(5- to 10-membered            heteroaryl)(C₁-C₁₀ heteroalkyl), —(C₁-C₄ alkyl)_(q)NH₂,            —(C₁-C₄ alkyl)_(q)CONH₂, —(C₁-C₄ alkyl)NHCONH₂, —(C₁-C₄            alkyl)NHCOH, —(C₁-C₄ alkyl)_(q)NHCOCH₃ or a group of formula            (III):

-   -   -   where B is —CH₂—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH(CH₃)—CH₂— or            —CH₂—CH(CH₃)—, and each q is 0 or 1; and        -   each X₂ is independently —H, —OH, —(C₁-C₁₀ alkyl), —(C₁-C₁₀            heteroalkyl), —(C₃-C₈ cycloalkyl), -(aryl), -(5- to            10-membered heteroaryl), —(C₁-C₁₀ alkyl)(aryl),            -(aryl)(C₁-C₁₀ alkyl), —(C₁-C₄ alkyl)_(q)NH₂, —(C₁-C₄            alkyl)_(q)CONH₂, —(C₁-C₄ alkyl)NHCONH₂, —(C₁-C₄            alkyl)_(q)NHCOH or —(C₁-C₄ alkyl)_(q)NHCOCH₃, where each q            is 0 or 1; or

    -   mixtures thereof;        (f) provided that when x is 1 and y is 0, M₁ is not        N-vinylacetamide, N-vinylpropamide, N-vinylbutamide or        N-vinylpentamide.

In certain embodiments, x is 1 and y is 0.

In certain embodiments, x is 2 and y is 0.

In certain embodiments, x is 3 and y is 0.

In certain embodiments, x is 4 and y is 0.

In certain embodiments, x is 5 and y is 0.

In certain embodiments, x is 1 and y is 1.

In certain embodiments, x is 2 and y is 1.

In certain embodiments, x is 3 and y is 1.

In certain embodiments, x is 4 and y is 1.

In certain embodiments, x is 5 and y is 1.

In certain embodiments, x is 1 and y is 2.

In certain embodiments, x is 2 and y is 2.

In certain embodiments, x is 3 and y is 2.

In certain embodiments, x is 4 and y is 2.

In certain embodiments, x is 5 and y is 2.

In certain embodiments, x is 1 and y is 3.

In certain embodiments, x is 2 and y is 3.

In certain embodiments, x is 3 and y is 3.

In certain embodiments, x is 4 and y is 3.

In certain embodiments, x is 5 and y is 3.

In certain embodiments, x is 1 and y is 4.

In certain embodiments, x is 2 and y is 4.

In certain embodiments, x is 3 and y is 4.

In certain embodiments, x is 4 and y is 4.

In certain embodiments, x is 5 and y is 4.

In certain embodiments, x is 1 and y is 5.

In certain embodiments, x is 2 and y is 5.

In certain embodiments, x is 3 and y is 5.

In certain embodiments, x is 4 and y is 5.

In certain embodiments, x is 5 and y is 5.

In certain embodiments, y is 0 and, for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl.

In other embodiments y is 0 and, for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H;    -   each R₃, R₄ and R₅ is independently H or methyl.

In another embodiment, y is 0 and, for each monomer subtype of type M₁:

-   -   A₁ is 0; and    -   R₁, R₂, R₃, R₄ and R₅ are H.

In another embodiment, y is 0 and, for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁, R₂, R₃, and R₄ are H; and    -   R₅ is methyl.

In another embodiment, y is 0 and, for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁, R₂ and R₃ are H; and    -   R₄ and R₅ are methyl.

In certain embodiments, y is 0, x is 2 and, for each monomer subtype oftype M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl.

In other embodiments, y is 0, x is 2 and, for each monomer subtype oftype M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H;    -   each R₃, R₄ and R₅ is independently H or methyl.

In another embodiment, y is 0, x is 2 and, for each monomer subtype oftype M₁:

-   -   A₁ is 0; and    -   R₁, R₂, R₃, R₄ and R₅ are H.

In another embodiment, y is 0, x is 2 and, for each monomer subtype oftype M₁:

-   -   A₁ is O;    -   R₁, R₂, R₃, and R₄ are H; and    -   R₅ is methyl.

In another embodiment, y is 0, x is 2 and, for each monomer subtype oftype M₁:

-   -   A₁ is O;    -   R₁, R₂ and R₃ are H; and    -   R₄ and R₅ are methyl.

In certain embodiments, y is 0, x is 1 and, for M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl.

In other embodiments, y is 0, x is 1 and, for M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H;    -   each R₃, R₄ and R₅ is independently H or methyl.

In another embodiment, y is 0, x is 1 and, for M₁:

-   -   A₁ is 0; and    -   R₁, R₂, R₃, R₄ and R₅ are H.

In another embodiment, y is 0, x is 1 and, for M₁:

-   -   A₁ is O;    -   R₁, R₂, R₃, and R₄ are H; and    -   R₅ is methyl.

In another embodiment, y is 0, x is 1 and, for M₁:

-   -   A₁ is O;    -   R₁, R₂ and R₃ are H; and    -   R₄ and R₅ are methyl.

In certain embodiments:

(a) for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (b) y is 2; and        (c) for each monomer subtype of type M₂ of formula (II):    -   A₂ is O;    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In certain embodiments:

(a) for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (b) y is 1; and        (c) for M₂ of formula (II):    -   A₂ is O;    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In certain embodiments:

(a) x is 2;

(b) for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (c) y is 2; and        (d) for each monomer subtype of type M₂ of formula (II):    -   A₂ is O;    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In certain embodiments:

(a) x is 2;

(b) for each monomer subtype of type M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (c) y is 1; and        (d) for M₂ of formula (II):    -   A₂ is O;    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In certain embodiments:

(a) x is 1;

(b) for M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (c) y is 2; and        (d) for each monomer subtype of type M₂ of formula (II):    -   A₂ is O;    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In certain embodiments:

(a) x is 1;

(b) for M₁:

-   -   A₁ is O;    -   R₁ and R₂ are H; and    -   each R₃ is independently H or methyl;        (c) y is 1; and        (d) for M₂ of formula (II):    -   A₂ is O;    -   R₆ and R₇ are H; and    -   each R₈ is independently H or methyl.

In some embodiments, a composition of the invention is free ofcrosslinked polymers. In some embodiments, a composition of theinvention is substantially free of crosslinked polymers.

In some embodiments, M₁, or each monomer subtype of type M₁ if x>1, isN-vinylformamide, N-vinylacetamide, N-vinylpropamide, N-vinylbutamide,N-vinylpentamide, N-vinylhexamide, N-vinylheptamide, N-vinyloctamide,N-vinylnonamide, N-vinyldecamide, N-methyl-N-vinylformamide,N-methyl-N-vinylacetamide, N-methyl-N-vinylpropamide,N-methyl-N-vinylbutamide, N-methyl-N-vinylpentamide,N-methyl-N-vinylhexamide, N-methyl-N-vinylheptamide,N-methyl-N-vinyloctamide, N-methyl-N-vinylnonamide,N-methyl-N-vinyldecamide, N-ethyl-N-vinylformamide,N-ethyl-N-vinylacetamide, N-ethyl-N-vinylpropamide,N-ethyl-N-vinylbutamide, N-ethyl-N-vinylpentamide,N-ethyl-N-vinylhexamide, N-ethyl-N-vinylheptamide,N-ethyl-N-vinyloctamide, N-ethyl-N-vinylnonamide,N-ethyl-N-vinyldecamide, N-n-propyl-N-vinylformamide,N-n-propyl-N-vinylacetamide, N-n-propyl-N-vinylpropamide,N-n-propyl-N-vinylbutamide, N-n-propyl-N-vinylpentamide,N-n-propyl-N-vinylhexamide, N-n-propyl-N-vinylheptamide,N-n-propyl-N-vinyloctamide, N-n-propyl-N-vinylnonamide,N-n-propyl-N-vinyldecamide, N-iso-propyl-N-vinylformamide,N-iso-propyl-N-vinylacetamide, N-iso-propyl-N-vinylpropamide,N-iso-propyl-N-vinylbutamide, N-iso-propyl-N-vinylpentamide,N-iso-propyl-N-vinylhexamide, N-iso-propyl-N-vinylheptamide,N-iso-propyl-N-vinyloctamide, N-iso-propyl-N-vinylnonamide,N-iso-propyl-N-vinyldecamide, or a mixture thereof.

In some embodiments, M₁, or each monomer subtype of type M₁ if x>1, isN-vinylformamide, N-vinylpropamide, N-vinylbutamide, N-vinylpentamide,N-vinylhexamide, N-vinylheptamide, N-vinyloctamide, N-vinylnonamide,N-vinyldecamide, N-methyl-N-vinylformamide, N-methyl-N-vinylacetamide,N-methyl-N-vinylpropamide, N-methyl-N-vinylbutamide,N-methyl-N-vinylpentamide, N-methyl-N-vinylhexamide,N-methyl-N-vinylheptamide, N-methyl-N-vinyloctamide,N-methyl-N-vinylnonamide, N-methyl-N-vinyldecamide,N-ethyl-N-vinylformamide, N-ethyl-N-vinylacetamide,N-ethyl-N-vinylpropamide, N-ethyl-N-vinylbutamide,N-ethyl-N-vinylpentamide, N-ethyl-N-vinylhexamide,N-ethyl-N-vinylheptamide, N-ethyl-N-vinyloctamide,N-ethyl-N-vinylnonamide, N-ethyl-N-vinyldecamide,N-n-propyl-N-vinylformamide, N-n-propyl-N-vinylacetamide,N-n-propyl-N-vinylpropamide, N-n-propyl-N-vinylbutamide,N-n-propyl-N-vinylpentamide, N-n-propyl-N-vinylhexamide,N-n-propyl-N-vinylheptamide, N-n-propyl-N-vinyloctamide,N-n-propyl-N-vinylnonamide, N-n-propyl-N-vinyldecamide,N-iso-propyl-N-vinylformamide, N-iso-propyl-N-vinylacetamide,N-iso-propyl-N-vinylpropamide, N-iso-propyl-N-vinylbutamide,N-iso-propyl-N-vinylpentamide, N-iso-propyl-N-vinylhexamide,N-iso-propyl-N-vinylheptamide, N-iso-propyl-N-vinyloctamide,N-iso-propyl-N-vinylnonamide, N-iso-propyl-N-vinyldecamide, or a mixturethereof.

In some embodiments, y is 0 and M₁, or each monomer subtype of type M₁if x>1, is N-vinylhexamide, N-vinylheptamide, N-vinyloctamide,N-vinylnonamide, N-vinyldecamide, N-methyl-N-vinylformamide,N-methyl-N-vinylacetamide, N-methyl-N-vinylpropamide,N-methyl-N-vinylbutamide, N-methyl-N-vinylpentamide,N-methyl-N-vinylhexamide, N-methyl-N-vinylheptamide,N-methyl-N-vinyloctamide, N-methyl-N-vinylnonamide,N-methyl-N-vinyldecamide, N-ethyl-N-vinylformamide,N-ethyl-N-vinylacetamide, N-ethyl-N-vinylpropamide,N-ethyl-N-vinylbutamide, N-ethyl-N-vinylpentamide,N-ethyl-N-vinylhexamide, N-ethyl-N-vinylheptamide,N-ethyl-N-vinyloctamide, N-ethyl-N-vinylnonamide,N-ethyl-N-vinyldecamide, N-n-propyl-N-vinylformamide,N-n-propyl-N-vinylacetamide, N-n-propyl-N-vinylpropamide,N-n-propyl-N-vinylbutamide, N-n-propyl-N-vinylpentamide,N-n-propyl-N-vinylhexamide, N-n-propyl-N-vinylheptamide,N-n-propyl-N-vinyloctamide, N-n-propyl-N-vinylnonamide,N-n-propyl-N-vinyldecamide, N-iso-propyl-N-vinylformamide,N-iso-propyl-N-vinylacetamide, N-iso-propyl-N-vinylpropamide,N-iso-propyl-N-vinylbutamide, N-iso-propyl-N-vinylpentamide,N-iso-propyl-N-vinylhexamide, N-iso-propyl-N-vinylheptamide,N-iso-propyl-N-vinyloctamide, N-iso-propyl-N-vinylnonamide,N-iso-propyl-N-vinyldecamide, or a mixture thereof.

In some embodiments, M₁, or each monomer subtype of type M₁ if x>1, isN-vinylformamide, N-vinylacetamide, N-vinylpropamide, N-vinylbutamide,N-methyl-N-vinylformamide, N-methyl-N-vinylacetamide,N-methyl-N-vinylpropamide, N-methyl-N-vinylbutamide,N-ethyl-N-vinylformamide, N-ethyl-N-vinylacetamide,N-ethyl-N-vinylpropamide, N-ethyl-N-vinylbutamide,N-n-propyl-N-vinylformamide, N-n-propyl-N-vinylacetamide,N-n-propyl-N-vinylpropamide, N-n-propyl-N-vinylbutamide,N-iso-propyl-N-vinylformamide, N-iso-propyl-N-vinylacetamide,N-iso-propyl-N-vinylpropamide, N-iso-propyl-N-vinylbutamide, or amixture thereof.

In other embodiments, M₂, or each monomer subtype of type M₂ if y>1, isone of the groups set forth in Section 4.1 of the Detailed Descriptionof the Invention. In other embodiments, in each of such embodiments forM₂, each M₁, or each monomer subtype of type M₁ if x>1, is independentlyN-vinylformamide, N-vinylacetamide or N-methyl-N-vinylacetamide or,alternatively, each M₁, or each monomer subtype of type M₁ if x>1, isindependently N-vinylformamide or N-methyl-N-vinylacetamide.

In other embodiments, the polymer of the invention is a copolymer thatis poly(N-vinylformamide-co-acrylamide);poly(N-vinylformamide-co-N-methyl-acrylamide);poly(N-vinylformamide-co-N,N-dimethyl-acrylamide);poly(N-vinylformamide-co-N-methoxymethyl-acrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-acrylamide);poly(N-vinylformamide-co-methacrylamide);poly(N-vinylformamide-co-N-methyl-methacrylamide);poly(N-vinylformamide-co-N,N-dimethyl-methacrylamide);poly(N-vinylformamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-vinylformamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-vinylformamide-co-vinyl acetate); poly(N-vinylformamide-co-vinylacetate-co-vinyl alcohol); poly(N-vinylacetamide-co-acrylamide);poly(N-vinylacetamide-co-N-methyl-acrylamide);poly(N-vinylacetamide-co-N,N-dimethyl-acrylamide);poly(N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-vinylacetamide-co-N-2-hydroxyethyl-acrylamide);poly(N-vinylacetamide-co-methacrylamide);poly(N-vinylacetamide-co-N-methyl-methacrylamide);poly(N-vinylacetamide-co-N,N-dimethyl-methacrylamide);poly(N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylacetamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-vinylacetamide-co-vinyl acetate); poly(N-vinylacetamide-co-vinylacetate-co-vinyl alcohol);poly(N-methyl-N-vinylacetamide-co-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-dimethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-methyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-dimethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-methyl-N-vinylacetamide-co-vinyl acetate);poly(N-methyl-N-vinylacetamide-co-vinyl acetate-co-vinyl alcohol); orsalts thereof.

In other embodiments, the polymer of the invention is a copolymer thatis poly(N-vinylformamide-co-acrylamide);poly(N-vinylformamide-co-N,N-dimethyl-acrylamide);poly(N-vinylformamide-co-N-methoxymethyl-acrylamide);poly(N-vinylformamide-co-methacrylamide);poly(N-vinylformamide-co-N,N-dimethyl-methacrylamide);poly(N-vinylformamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylformamide-co-1-vinyl-pyrrolidine-2, 5-dione);poly(N-vinylformamide-co-vinyl acetate);poly(N-vinylacetamide-co-acrylamide);poly(N-vinylacetamide-co-N,N-dimethyl-acrylamide);poly(N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-vinylacetamide-co-methacrylamide); poly(N-vinylacetamide-co-N,N-dimethyl-methacrylamide);poly(N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-vinylacetamide-co-vinyl acetate);poly(N-methyl-N-vinylacetamide-co-acrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-dimethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-dimethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-methyl-N-vinylacetamide-co-vinyl acetate); or salts thereof.

In other embodiments, the polymer of the invention is a copolymer thatis poly(N-vinylformamide-co-acrylamide);poly(N-vinylformamide-co-N-methyl-acrylamide);poly(N-vinylformamide-co-N,N-dimethyl-acrylamide);poly(N-vinylformamide-co-N-methoxymethyl-acrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-acrylamide);poly(N-vinylformamide-co-methacrylamide);poly(N-vinylformamide-co-N-methyl-methacrylamide);poly(N-vinylformamide-co-N,N-dimethyl-methacrylamide);poly(N-vinylformamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylformamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-vinylformamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-vinylformamide-co-vinyl acetate); poly(N-vinylformamide-co-vinylacetate-co-vinyl alcohol);poly(N-methyl-N-vinylacetamide-co-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-dimethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-methyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-dimethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-2-hydroxyethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-methyl-N-vinylacetamide-co-vinyl acetate);poly(N-methyl-N-vinylacetamide-co-vinyl acetate-co-vinyl alcohol); orsalts thereof.

In other embodiments, the polymer of the invention is a copolymer thatis poly(N-vinylformamide-co-acrylamide);poly(N-vinylformamide-co-N,N-dimethyl-acrylamide);poly(N-vinylformamide-co-N-methoxymethyl-acrylamide);poly(N-vinylformamide-co-methacrylamide);poly(N-vinylformamide-co-N,N-dimethyl-methacrylamide);poly(N-vinylformamide-co-N-methoxymethyl-methacrylamide);poly(N-vinylformamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-vinylformamide-co-vinyl acetate);poly(N-methyl-N-vinylacetamide-co-acrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-dimethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-acrylamide);poly(N-methyl-N-vinylacetamide-co-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N,N-dimethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-N-methoxymethyl-methacrylamide);poly(N-methyl-N-vinylacetamide-co-1-vinyl-pyrrolidine-2,5-dione);poly(N-methyl-N-vinylacetamide-co-vinyl acetate); or salts thereof.

In some embodiments, compositions of the invention can suppress oreliminate electroosmosis or electroosmotic flow (“EOF”), which refers tocapillary-fluid flow induced by an electrical field. In addition,compositions of the invention can provide excellent electrophoreticresolution.

In some embodiments, compositions of the invention comprise an effectiveamount of a polymer of the invention. For the purposes of thisapplication, an “effective amount of a polymer of the invention” meansthat the polymer is present in an amount or concentration sufficient toseparate a biomolecule from at least one other molecule, e.g., an amounteffective to cause at least two biomolecule components of a samplemixture to have different mobilities in CE. The weight fraction of apolymer of the invention present in a composition of the invention,based on the total weight of composition, is from about 0.0001 to about0.02. In another embodiment, the weight fraction of the polymer of theinvention present in a composition of the invention is from about 0.001to about 0.015. In another embodiment, the weight fraction of thepolymer of the invention present in a composition of the invention isfrom about 0.001 to about 0.005.

4.3.1. Buffer

The present compositions comprise a buffer for controlling pH. In oneembodiment, the buffer is an aqueous buffer. In another embodiment, thebuffer is a substantially dry buffer. In another embodiment, the bufferis a dry buffer. In another embodiment, the buffer provides a bufferedcomposition with a pH of from about 5 to about 11. In anotherembodiment, the buffer provides a buffered composition with a pH of fromabout 7 to about 10. Exemplary aqueous buffers include aqueous solutionsof organic acids, such as citric, acetic or formic acid; zwitterionics,such as N-tris(hydroxymethyl)-2-aminoethane sulfonic acid (“TES”),N,N-bis-(2-hydroxyethyl)glycine (“BICINE”),2-(2-amino-2-oxoethyl)-amino)ethane sulfonic acid (“ACES”) orglycylglycine; inorganic acids, such as phosphoric acid; and organicbases, such as TRIS. Exemplary substantially dry buffers can be preparedfrom each of the above aqueous buffers by substantially evaporating thewater. Exemplary dry buffers can be prepared from each of the aboveaqueous buffers by completely evaporating the water.

Buffer concentration can vary widely, for example from about 1 mmol toabout 1 mol, and often about 20 mmol/liter of water is used. Exemplarybuffer solutions for conventional CE applications include the following:0.1 M TRIS, 0.25 M boric acid, 7 M urea with a pH of about 7.6 forsingle stranded polynucleotide separations; or 0.089 M TRIS, 0.089 Mboric acid, 0.005 M ethylenediamine tetraacetic acid (“EDTA”) for doublestranded polynucleotide separations.

In another embodiment, the buffers include “GA” buffer, “TTE” buffer, ora mixture thereof. GA buffer comprises3-((2-hydroxy-1,1-bis-(hydroxymethyl)ethyl))-amino)-1-propanesulfonicacid sodium salt (“TAPS”) and EDTA with from about 1 to about 4 mM ofEDTA present per 100 mM of TAPS such that the pH of the buffer is about8.0. In another embodiment, the GA buffer can be used in a concentratedform, i.e., 10×GA buffer, which comprises from about 10 to about 40 mMof EDTA present per 100 mM of TAPS. TTE buffer comprises TRIS, TAPS andEDTA with about 1 mM of EDTA present per 50 mM of TRIS plus 50 mM ofTAPS such that the pH of the buffer is about 8.4. In another embodiment,the TTE buffer can be used in a concentrated form, i.e., 10×TTE buffer,which comprises about 10 mM of EDTA present per 500 mM of TRIS plus 500mM of TAPS.

An effective concentration of aqueous buffer present in a composition ofthe invention is from about 10 mM to about 300 mM. In one embodiment,the effective concentration of aqueous buffer is from about 25 mM toabout 200 mM. In another embodiment, the concentration of aqueous bufferpresent in a composition of the invention is from about 50 mM to about100 mM.

In another embodiment, an aqueous composition of the invention isuncrosslinked. In another embodiment, an aqueous composition of theinvention is substantially uncrosslinked.

4.3.2. Sieve and/or EOF Suppressing Polymer

In some embodiments, for CE, compositions of the invention can provideuseful sieving and/or EOF suppression functions to facilitate theseparations of biomolecules such as polynucleotides. Whether acomposition of the invention provides sieving or EOF suppression or bothwill depend on the amount or concentration of polymer that is present,whether a plurality of polymers are present and their relative amountsor concentrations, and other factors. For example, use of a polymer ofthe invention at a low concentration may be effective to suppress EOFbut may not provide significant sieving. However, another polymer, i.e.,a sieve and/or EOF suppressing polymer, can be included to provide asieving function. Alternatively, a polymer of the invention can providea sieving function but another polymer, i.e., a sieve and/or EOFsuppressing polymer, can be included, usually at a smallerconcentration, to suppress EOF if so desired. In yet another example,two or more polymers can be included in a composition of the invention(including at least one polymer of the invention) and the polymers cancontribute to sieving, or to EOF suppression, or to both. For example,two different polymers may be present, each at a concentration thatalone is insufficient for significant sieving, but such that the sum ofthe two polymers together provide a desired level of sieving. In yetanother example, a single polymer of the invention provides both sievingand EOF suppression that is adequate for a particular electrophoreticseparation.

In one embodiment, when present, the sieve and/or EOF suppressingpolymer at least one of the dynamic, static or hybrid polymer wallcoatings for CE. For example, those polymers and copolymers disclosed inJ. Horvath et al., Electrophoresis, 22:644-655 (2001), can be used, suchas poly(n-undecyl-α-D-glucopyranoside) (PUG), polyoxyethylene ether(BRIJ-35®), poly(dimethyldiallylammonium chloride) (PDMAC),poly(ethyleneimine) (PEI), polybrene (PB), poly(arginine) (PA), dextran,cationiccylodextran, 40-140 nm polystyrene particles derivatized withα-ω diamines, 40-140 nm polystyrene particles derivatized with α-ωdiamines wherein the amino functionality is derivatized with2,3-epoxy-1-propanol, poly(vinyl alcohol) (PVA), alkylene-glycolpolymers, poly(N-vinylpyrrolidone) (PVP), copolymers of vinylpyrrolidoneand vinylimidazole, poly(ethylene oxide) (PEO), (polyethyleneoxide-polypropylene oxide-polyethylene oxide) triblock copolymer,poly(N-isopropyl acrylamide)-g-poly(ethylene oxide), poly(acrylamide),cross-linked polyacrylamide (acrylamide+bisacrylamide),poly(acrylamide-co-allyl α-D-glucopyranoside) (poly(AG-AA)),poly(acrylamide-co-allyl α-D-glucopyranoside-co-allylglycidyl ether)(epoxypoly(AG-AA)), poly(N,N′-dimethylacrylamide) (PDMA), copolymers ofN,N′-dimethylacrylamide, such aspoly(N,N′-dimethylacrylamide-co-allylglycidyl ether) (EPPDMA), graftcopolymers of N,N′-dimethylacrylamide, poly(N-acryloylaminoethoxyethanol) (polyAAEE), poly(N-acryloylaminopropanol) (polyAAP),poly(acryloyldiethanolamine), poly(2-aminoethyl methacrylatehydrochloride) (PALM), hydrophilic poly(ethylene glycol) (PEG),polyamide resin, polyamine (i.e., eCAP®), poly(vinylamine),sodium-2-acrylamido-2-methylpropanesulfonate (NaAMPS), fibrinogen,cellulose acetate, cellulose triacetate, methylcellulose (MC),hydroxypropylmethlylcellulose, hydroxyethylcellulose (HEC), cross-linkedhydroxypropylcellulose (HPC), epoxybutane-modifiedhydroxyproplylcellulose (EB-HPC), and a copolymer of HPC and2-hydroxyethyl methacrylate.

Optionally, in some embodiments, compositions of the invention canadditionally comprise one or more sieve polymers, present in aneffective amount. Without being bound by theory, a primary CE separationmechanism for different sized biomolecules, e.g., polynucleotides, isdetermined by their charge-to-frictional drag ratio. Thus, it isdesirable that a sieve polymer is present if, in the absence of thesame, two or more biomolecules would co-migrate in CE, i.e., move withabout the same mobility. For the purposes of this application, an“effective amount of a sieve polymer” an “effective amount of an EOFsuppressing polymer” and an “effective amount of a sieve and/or EOFsuppressing polymer” means an amount effective to cause at least twobiomolecule components of a sample mixture to have different mobilitiesin CE.

In some embodiments, compositions of the invention contain gelled orcrosslinked polymers that provide sieving and/or EOF suppressionproperties. In other embodiments, compositions of the invention containnon-covalently-crosslinked sieve and/or EOF suppressing polymerscomprising any or all of hydroxyalkylcellulose, agarose, celluloseacetate, linear polyacrylamide (“PAAm”) and the like, as disclosed by,e.g., Bode, Anal. Biochem., 83:204-210 (1977); Bode, Anal. Biochem.,83:364-371 (1977); Bode, Anal. Biochem., 92:99-110 (1979); Hjerten etal., J. Liquid Chromatography, 12:2471-2477 (1989); U.S. Pat. No.5,126,021 to Grossman; and Tietz et al., Electrophoresis, 13:614-616(1992).

In some embodiments, when present in the compositions of the invention,the sieve and/or EOF suppressing polymer is one or more substantiallyuncrosslinked polymers. In another embodiment, the sieve and/or EOFsuppressing polymer is one or more substantially linear polymers.

In another embodiment, the sieve and/or EOF suppressing polymer is watersoluble at atmospheric pressure, a concentration of from about 0.01 toabout 1 wt. %, and from about 20° C. to about 70° C. In anotherembodiment, the sieve and/or EOF suppressing polymer is water soluble atatmospheric pressure, a concentration of from about 0.01 to about 1 wt.%, and at about 25° C.

In one embodiment, when a sieve and/or EOF suppressing polymer ispresent in the compositions of the invention, the sieve and/or EOFsuppressing polymer has an Mw of from about 100,000 Da to about 5 MDa.In another embodiment, the sieve and/or EOF suppressing polymer has anMw of from about 500,000 Da to about 2 MDa. In another embodiment, thesieve and/or EOF suppressing polymer, when present, has an Mw of fromabout 800,000 Da to about 2 MDa.

In one embodiment, the sieve and/or EOF suppressing polymer comprises amonomer unit that is acrylamide, N-acetyl-acrylamide,N-2-cyanoethyl-acrylamide, N,N-1,2-dihydroxyethylene-bis-acrylamide,N-4,4-dimethoxybutyl-acrylamide, N-2,2-dimethoxyethyl-acrylamide,N,N-dimethyl-acrylamide, N-2-glycolic acid methyl ester acrylamide,N-2-hydroxyethyl-acrylamide, N-hydroxymethyl-acrylamide,N-methoxymethyl-acrylamide, N-3-methoxypropyl-acrylamide,N-methyl-acrylamide, N-methyl-, N-2,2-dimethoxyethyl-acrylamide,N-morpholinoethyl-acrylamide,N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)-methyl-acrylamide, methacrylamide,N-acetyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N,N-1,2-dihydroxyethylene-bis-methacrylamide,N-4,4-dimethoxybutyl-methacrylamide,N-2,2-dimethoxyethyl-methacrylamide, N,N-dimethyl-methacrylamide,N-2-glycolic acid methyl ester methacrylamide,N-2-hydroxyethyl-methacrylamide, N-hydroxymethyl-methacrylamide,N-methoxymethyl-methacrylamide, N-3-methoxypropyl-methacrylamide,N-methyl-methacrylamide, N-methyl-, N-2,2-dimethoxyethyl-methacrylamide,N-morpholinoethyl-methacrylamide,N-2,2,2-trichloro-1-hydroxyethyl-methacrylamide, orN-tri(hydroxymethyl)-methyl-methacrylamide, or a mixture thereof.

In another embodiment, the sieve and/or EOF suppressing polymer ispoly(hydroxymethylene), poly(oxyethylene), poly(oxypropylene),poly(oxyethylene-co-oxypropylene), poly(vinyl alcohol),poly(vinylpyrrolidone), poly(2-ethyl-2-oxazoline),poly(2-methyl-2-oxazoline), poly((2-ethyl-2-oxazoline)-co-(2-methyl-2-oxazoline)),poly(N-acetamidoacrylamide), poly(acryloxylurea), a water-solublepolysaccharide such as hydroxyethyl cellulose or hydroxymethylcellulose, or a mixture thereof.

In one embodiment, the sieve and/or EOF suppressing polymer includes anacrylamide monomer unit. In another embodiment, at least about 80 mol %of the sieve and/or EOF suppressing polymer's monomer units areacrylamide units. In another embodiment, at least about 90 mol % of thesieve and/or EOF suppressing polymer's monomer units are acrylamideunits. In another embodiment, at least about 95 mol % of the sieveand/or EOF suppressing polymer's monomer units are acrylamide units. Inanother embodiment, the sieve and/or EOF suppressing polymer ispolyacrylamide that is substantially linear, i.e., in which the amountof branching is insignificant such that the solution viscosity of thatpolyacrylamide is not substantially different from the solutionviscosity of a substantially linear polyacrylamide having the same Mw.

When present, the weight fraction of sieve and/or EOF suppressingpolymer in a composition of the invention, based on the total weight ofthe composition, is from about 0.001 to about 0.1. In anotherembodiment, the weight fraction of sieve and/or EOF suppressing polymerin a composition of the invention is from about 0.005 to about 0.05. Inanother embodiment, the weight fraction of sieve and/or EOF suppressingpolymer present in a composition of the invention is from about 0.01 toabout 0.03 (0.01 wt. fraction=1 wt. %).

4.3.3. Denaturant

Additional optional components, such as denaturants, can be included inthe compositions of the invention, e.g., when it is desirable to preventthe formation of duplexes or secondary structures in polynucleotides. Inone embodiment, denaturants include formamide, urea, detergents such assodium dodecyl sulfate, and commercially available lactams, such aspyrrolidone and N-methyl pyrrolidone, as well as their mixtures. The useof denaturants in electrophoresis is conventional and is described in,e.g., recognized molecular biology references such as Sambrook et al.,Molecular Cloning: A Laboratory Manual, (Cold Spring Harbor Laboratory,New York, 2^(nd) Ed. 1989). In another embodiment, the denaturanit, whenpresent, is formamide, urea, pyrrolidone, N-methyl pyrrolidone, or amixture thereof. In another embodiment, the denaturant, when present, isurea. In another embodiment, the denaturant, when present, is formamide.

When present, the concentration of denaturant in a composition of theinvention is from about 0.5 M to about 8 M. In another embodiment, theconcentration of denaturant is from about 2 M to about 8 M. In anotherembodiment, the concentration of denaturant present in a composition ofthe invention is from about 6 M to about 8 M.

4.4. Methods for Making Compositions

A fourth embodiment of the invention relates to a method for making acomposition of the invention, comprising admixing a polymer of theinvention with a buffer. This method can further comprise admixing witha sieve and/or EOF suppressing polymer or a salt thereof and/or adenaturant. The compositions of the invention are useful aselectrophoresis separation media. For example, a composition of theinvention can be prepared by dissolving, at 25° C., a polymer of theinvention and, when it is present, the sieve and/or EOF suppressingpolymer or salt thereof, in water followed by adding a concentrated formof the buffer. Alternatively, the polymer of the invention can bedissolved directly in an aqueous buffer and, optionally, a sieve and/orEOF suppressing polymer can be added to that solution. The denaturantcan be present either before or after the optional sieve and/or EOFsuppressing polymer is added. Thus, the polymer of the invention, andthe sieve and/or EOF suppressing polymer when it is present, can beadded to water, aqueous buffer, water and denaturant, or aqueous bufferand denaturant, depending on which combination is selected for use.Moreover, when the sieve and/or EOF suppressing polymer is present, itcan be dissolved in, e.g., the buffer, before the polymer of theinvention is introduced. Any order of adding the components for making acomposition of the invention is within the scope of this embodiment ofthe invention.

4.5. Methods for Separating

In a fifth embodiment of the invention, the compositions of theinvention are useful in a method for detecting or separating a sample oranalyte, e.g., a biomolecule or mixture of biomolecules. As used herein,“analyte” includes the substance for which a particular sample is beingtested, e.g., for the presence and/or amount contained in the sample.

For example, a suitable method for separating a mixture of biomoleculesusing a composition of the invention comprises:

-   (a) contacting a composition of the invention with a mixture    comprising a biomolecule; and-   (b) applying an electric field to the composition in an amount    sufficient to facilitate the separation of a biomolecule from the    mixture.

In another embodiment, the composition of the invention furthercomprises a sieve and/or EOF suppressing polymer or a salt thereof. Inanother embodiment, the composition of the invention further comprises adenaturant. In another embodiment, the composition of the invention isin a support such as a capillary tube or column, prior to contactingwith a biomolecule.

The biomolecule(s) can be a polynucleotide or polynucleotides. In oneembodiment, biomolecules include proteins, glycoproteins, natural andsynthetic peptides, alkaloids, polysaccharides, polynucleotides, and thelike. In another embodiment, biomolecule refers to polynucleotides. Inanother embodiment, a biomolecule can be a polysaccharide. In anotherembodiment, a biomolecule can be a negatively-charged polysaccharide. Inanother embodiment, a biomolecule can be a carbohydrate. In anotherembodiment, a biomolecule can be a negatively-charged carbohydrate. Inanother embodiment, biomolecules can be a mixture comprising apolynucleotide, a polysaccharide and a carbohydrate. In anotherembodiment, biomolecules can be a mixture comprising a polynucleotideand a carbohydrate. In another embodiment, biomolecules can be a mixturecomprising a polynucleotide and a polysaccharide. In another embodiment,biomolecules can be a mixture comprising a polysaccharide and acarbohydrate.

The term “polynucleotide,” as used herein, refers to a linear polymer ofnatural or modified nucleoside monomers, including double and singlestranded deoxyribonucleosides, ribonucleosides, α-anomeric formsthereof, and the like. Usually the nucleoside monomers are linked byphosphodiester bonds or analogs thereof to form polynucleotides rangingin size from a few monomeric units, e.g., from about 8 to about 40, toseveral thousands of monomeric units. Whenever a polynucleotide isrepresented by a sequence of letters, such as “GTTACTG,” it will beunderstood that the nucleotides are in 5′→3′ order from left to rightand that “A” denotes deoxyadenosine, “C” denotes deoxycytidine, “G”denotes deoxyguanosine, and “T” denotes thymidine, unless otherwisenoted. Analogs of phosphodiester linkages include phosphorothioate,phosphorodithioate, phosphoroselenoate, phosphorodiselenoate,phosphoroanilothioate, phosphoranilidate, phosphoramidate, and the like.

As used herein, “nucleoside” includes the natural nucleosides, including2′-deoxy and 2′-hydroxyl forms, e.g., as described in Komberg and Baker,DNA Replication, 2nd Ed. (Freeman, San Francisco, 1992). “Analogs” inreference to nucleosides includes synthetic nucleosides having modifiedbase moieties and/or modified sugar moieties, e.g., described generallyby Scheit, Nucleotide Analogs (John Wiley, New York, 1980).

Regarding the degree of separation of a sample or analyte, it isconventional in CE that “resolution” or “Rs” is defined as:Rs=0.59(Y ₂ −Y ₁)/FWHM  (1)where Y₁ and Y₂ are the centers of two adjacent CE peaks and FWHM is thepeak width at half-height, assuming that both peaks have substantiallythe same width. (See, e.g., Albarghouthi, Electrophoresis, 21:4096-4111(2000)). As used herein, “crossover” is the number of base pairs for thebase pair whose (Y₂−Y₁) value is equal to its FWHM value. In otherwords, a crossover of 650 base pairs (“bp”) means that the resolution ofthe 650^(th) base pair is 0.59.

In one embodiment, in a method for separating a mixture of biomoleculesusing a composition of the invention, the method results in a crossoverof at least 400 bp. In another embodiment, in a method for separating amixture of biomolecules using a composition of the invention, the methodresults in a crossover of at least about 600 bp. In another embodiment,in a method for separating a mixture of biomolecules using a compositionof the invention, the method results in a crossover of at least about700 bp. In another embodiment, in a method for separating a mixture ofbiomolecules using a composition of the invention, the method results ina crossover of at least about 800 bp. In another embodiment, in a methodfor separating a mixture of biomolecules using a composition of theinvention, the method results in a crossover of at least about 900 bp.In another embodiment, in a method for separating a mixture ofbiomolecules using a composition of the invention, the method results ina crossover of at least about 1000 bp. In another embodiment, in amethod for separating a mixture of biomolecules using a composition ofthe invention, the method results in a crossover of at least about 1100bp. In another embodiment, in a method for separating a mixture ofbiomolecules using a composition of the invention, the method results ina crossover of at least about 1200 bp.

4.6. Electrophoresis Apparatus

An electrophoresis apparatus comprises a support, e.g., a capillary, fora composition of the invention. In one embodiment, the support definesan elongate channel connectable at opposite ends to opposing polarityterminals of a voltage source for containing a composition of theinvention, e.g., a separation medium. The term “capillary,” as usedherein, refers to a tube or channel or other structure capable ofsupporting a volume of composition of the invention useful for carryingout electrophoresis. The geometry of a support or capillary can varywidely and includes tubes with circular, rectangular or squarecross-sections, channels, groves, plates and the like, each of which canbe fabricated by a wide range of technologies. For example, the supportcan comprise a CE array of bundled capillary channels. Alternately, thesupport can be of the microfabricated type, such as a channel chemicallyetched into a glass wafer as described by, e.g., Liu et al., Anal.Chem., 71:566-573 (1999). Exemplary references describing CE microchipapparatuses include the previous citation and Woolley et al., Anal.Chem., 67:3676-3680 (1995), which discloses a CE microchip with aplurality of support channels, each measuring 50 μm wide and 8 μm deep.

An important feature of a support used with the composition of theinvention is the surface area-to-volume ratio of the support's innersurface that is in contact with the volume of the composition of theinvention. High values of this ratio permit better heat transfer fromthe composition during electrophoresis. In one embodiment, values in therange of from about 20,000 to about 200,000 are employed. Thesecorrespond to the surface area-to-volume ratios of tubular capillarieswith circular cross-sections having inside diameters of from about 200μm to about 10 μm.

In another embodiment, the support is a tubular capillary having alength of from about 10 to about 200 cm. In another embodiment, thesupport is a tubular capillary having a length of less than about 100cm. In another embodiment, the support is a tubular capillary having aninner diameter of from about 10 to about 200 μm. In another embodiment,the support is a tubular capillary having an inner diameter of fromabout 25 to about 75 μm.

Capillaries for the invention can be made of silica, fused silica,silicate-based glass, such as borosilicate glass, alumina-containingglass, phosphate glass, quartz and the like, or other silica-likematerials. In one embodiment, the capillary comprises fused silica. Thecapillary can be uncoated on its outside surface. In another embodiment,the capillary is coated on the outside surface with a polyimide layer,e.g., to provide sufficient mechanical strengthening and/or promote easeof handling. The capillary can be coated on its inside surface, with oneor a plurality of layers, typically with a silane-derived coating and/orPAAm as described in, e.g., U.S. Pat. No. 4,997,537 to Karger et al., atcol. 5, line 9 to col. 6, line 14. In another embodiment, the capillaryis uncoated on the inside surface.

Apparatuses for performing capillary electrophoresis are well-known.Several CE instruments are commercially available, e.g., the AppliedBiosystems Inc. (ABI, Foster City, Calif.) model 310 Genetic Analyzer,models 3700 and 3730 DNA Analyzer, and the ABI PRISM® 3100 GeneticAnalyzer. Exemplary references describing CE apparatus and theiroperation include Colburn et al., Applied Biosystems Research News,Issue 1 (Winter 1990); Grossman et al., Eds., Capillary Electrophoresis(Academic Press, San Diego, 1992); Harrison et al., Science, 261:895-897(1993); U.S. Pat. No. 4,908,112 to Pace; U.S. Pat. No. 5,192,412 toKambara et al.; and Seiler et al., Anal. Chem., 65:1481-1488 (1993).

Contacting a composition of the invention with the support such that thesupport contains the composition can be performed using conventionalmethods, e.g., by connecting one end to a syringe and injecting thecomposition into the support under a controlled pressure. When thesupport is a capillary, the injection pressure can range from about 50to about 800 psi. In another embodiment, the injection pressure for thecapillary support is from about 200 to about 400 psi. Alternately,contacting a composition of the invention with the support such that thesupport contains the composition can be performed by connecting thecapillary support to a filling tube and applying a nitrogen or heliumgas pressure of from about 100 to about 500 psi for from about 5 toabout 60 minutes, depending on the viscosity of the composition. U.S.Pat. No. 4,997,537 to Karger et al. discloses PAAm filling with a TEFLONtube and a syringe.

Another way for introducing a composition to the support so that thecomposition is contained therein is by immersing one of the two ends ofthe support into a reservoir containing a composition of the inventionand increasing the air pressure above that composition to greater thanatmospheric pressure, thereby forcing the composition into the supportvia positive pressure. Alternatively, the air pressure at the end of thesupport opposite to its immersed end can be reduced to belowatmospheric, thereby drawing the composition into the support bysuction.

Regardless of the method used, it is known in the art that the containedcomposition should fill the support substantially uniformly andhomogeneously, i.e., the composition should be substantially uniform indensity throughout the support and be substantially withoutdiscontinuities or voids. See, e.g., U.S. Pat. No. 5,468,365 to Menchenet al., col. 16, lines 33-45. The Brookfield viscosity of a compositionof the invention is suitably from about 100 to about 1000 cPs. Inanother embodiment, the Brookfield viscosity of a composition of theinvention is from about 200 to about 500 cPs. The compositions of theinvention are appropriately characterized by Method A of the ASTM D2196-99 test entitled “Standard Test Methods for Rheological Propertiesof Non-Newtonian Materials by Rotational (Brookfield type) Viscometer.”In this test and by “Method A” described therein, the apparent orBrookfield viscosity is determined by experimentally measuring thetorque on a spindle rotating at a constant speed within the liquidcomposition at a temperature of 25° C. Spindle No. 00 is used at arotational speed of 10 rpm in a Brookfield Model RV Viscometer or itsequivalent for all of these experiments.

A sixth embodiment of the invention relates to a support containing acomposition of the invention. In another embodiment, the support is acapillary. In another embodiment, the capillary is a capillary tube.

In another embodiment, when multiple CE runs are conducted for a givencomposition/analyte combination, the composition is substantiallyremoved, i.e., 99%, removed from the capillary at the completion of eachCE run and a fresh aliquot of the composition is introduced before thestart of the next CE run. In another embodiment, the entire removal andfilling operation is conducted under automatic control, e.g., to promotereliable and reproducible CE results.

A cathodic reservoir can contain the composition into which a cathodeand the cathodic end of the capillary are immersed duringelectrophoresis, except for the brief period of time in which the sampleis added. The air pressure above the composition can be controlled,e.g., for loading the composition into the capillary by positivepressure. An anodic reservoir can contain the composition into which ananode and the anodic end of the capillary is immersed duringelectrophoresis. The air pressure above that portion of the compositioncan also be controlled, if desired e.g., for drawing the compositioninto the capillary under reduced pressure. In another embodiment, thecomposition in the cathodic reservoir is about the same as thecomposition in the anodic reservoir. The entire CE apparatus ismaintained at a preselected constant temperature throughout a separationrun.

A high-voltage source is connected between the cathode and anode suchthat a run potential in the range of from about 2 to about 60 kV isproduced across the electrodes throughout CE. In another embodiment, thepotential is in the range of from about 5 to about 20 kV. Alternatively,or in addition, a selected-frequency pulsed voltage can be appliedbetween the electrodes, if desired. Currents through the capillaryduring the CE run can be in the microamp range, typically from about 2to about 100 μA. In another embodiment, currents through the capillaryduring the CE run are from about 5 to about 30 μA.

A sample or analyte to be analyzed using CE comprises a mixture ofbiomolecules. To begin a CE run, the sample and the composition of theinvention can be contacted by any known means, e.g., by syringe layeringinjection or differential pressure. In another embodiment, the sample isadded by electrokinetic injection, e.g., by placing the cathode andcathodic end of the capillary into a sample solution then applying aninjection potential and current across the capillary for a short time.The sample can be electrokinetically injected for about 3 to about 150seconds under a potential of from about 0.5 to about 18 kV. Separationcan commence after returning the cathode and cathodic end of thecapillary into the cathode reservoir and application of the runpotential and current.

An on-line detector positioned adjacent to capillary and nearer to itsanodic end monitors separated bands of sample migrating through adetection zone of the capillary. Typically, an optical detection zonecomprises a region of capillary in which any outer coating has beenremoved to allow UV and/or visible light, e.g. fluorescence, detectionof the separated analyte. However, a wide variety of detection schemesare can be used with the invention, including UV absorbance,fluorescence emission, laser-induced fluorescence, conductance,radioactive emission and the like. For example, detection systems forfluorescent analytes are described in U.S. Pat. No. 4,675,300 to Zare etal. and U.S. Pat. No. 4,548,498 to Folestad et al. Alternately, a4-color detection system, such as is conventional in DNA analysis,utilizing an argon ion laser as a fluorescence-excitation light sourcethat emits light at wavelengths of 488 and 514 nm used in conjunctionwith a charged coupled device detector has be described in U.S. Pat. No.5,916,426 to Madabhushi et al.

Prior to its use with a different analyte and/or composition, thecapillary can be flushed, e.g., with 20 column volumes of water, 20column volumes tetrahydrofuran (THF), 20 column volumes 1 M NaOH and 20column volumes of water, before a composition of the invention is addedto it. In order to provide, e.g., reliable and reproducible CE results,in one embodiment the used capillary is replaced with an unusedcapillary containing fresh composition and the sample is added byelectrokinetic injection, as described above.

5. EXAMPLES

As noted above, the polymer of the invention yield advantageous CEperformance in the analysis and separation of biomolecules. Thefollowing examples further illustrate certain embodiments of the presentinvention. These examples are provided solely for illustrative purposesand in no way limit the scope of the present invention.

5.1. Preparation of Illustrative Compositions of the InventionComprising PVF

A series of three compositions, IC₁-3, comprised poly(N-vinylformamide)(“PVF”). Each of these compositions also comprisedpoly(N,N-dimethylacrylamide) (“PDMA”). The weight percent for each ofthe components present in each composition is provided in Table 1.

TABLE 1 Illustrative Compositions of the Invention Comprising PVFComposition Designation IC1 IC2 IC3 PVF Mw 2559 kDa 1238 kDa 1125 kDaPVF Amount 2.23% 2.21% 2.17% 10X TTE Buffer Amount 8.91% 8.94% 10.70%Urea Amount 37.88% 38.02% 37.21% MILLI-Q Water Amount 50.77% 50.63%49.73% PDMA^(a) Amount 0.21% 0.20% 0.20% ^(a)Mw = 984 kDa, Mn = 315 kDa

Each of IC1-IC3 was prepared using substantially linear PDMA of Mw about984 kDa and Mn about 315 kDa, as determined by GPC-MALLS, that wasdialyzed and lyophilized prior to its use. PDMA was also included toreduce EOF. The PDMA was dialyzed with 50K MWCO Spectra/Por-7regenerated cellulose membranes for 4 days with two changes of water (5gallons each) and lypophilized prior to its use. The water used in eachof IC1-3 was purified using a MILLI-Q Water System (Millipore Corp.,Bedford, Mass.).

The Brookfield viscosity of each composition, as measured by Method A ofthe ASTM D 2196-99 test discussed above, ranged from about 300 to about500 centipoise. It was observed that, in general, the lower themolecular weight of the PVF used, the lower was the viscosity of thecomposition.

5.2. Capillary Electrophoresis of DNA Using Compositions Comprising PVF

Compositions comprising an illustrative polymer of the invention wereevaluated for their usefulness as capillary electrophoresis separationmedia in DNA sequencing. In the following examples, each composition ofthe invention was evaluated in CE by using an ABI 310 Genetic Analyzerequipped with a 47 cm long by 50 μm inner diameter uncoated fused silicacapillary.

In each comparative separation medium (“CSM”) “control,” either GAbuffer or TTE buffer was used. Urea denaturant was also present. Eachseparation medium was prepared by dissolving, at 25° C., the polymericcomponents in a solution of buffer and denaturant.

CE sequencing runs for the separation media were conducted in thepresence of a ladder of TET-dye labeled fragments, having lengths of 35,50, 75, 100, 139, 150, 160, 200, 250, 300, 340, 350, 400, 450, 490, 500,550, 600, 650 and 700 base pairs, at several temperatures, usually 50,60 and 70° C., with 1.5 kV injection voltage and 10 sec injection timeand with 9.5 kV run voltage. The crossover and run time were determinedat each temperature.

The composition and CE sequencing performance data, from an average ofdata from four CE runs, for the separation media are summarized in Table2.

TABLE 2 CE Crossover and Run Time of Compositions of the Invention PDMACrossover (bp) Run Time for 700 bp (min) PVF (984 kDa) 50° C. 60° C. 70°C. 50° C. 60° C. 70° C. IC1 2.23 wt % 0.21 wt % 620 615 485 54.7 51.249.4 IC2 2.21 wt % 0.20 wt % 614 588 545 51.2 47.7 46.3 IC3 2.17 wt %0.20 wt % 590 552 482 47.1 43.2 40.9

The results in Table 2 demonstrate that the run times of each of IC1,IC2 and IC3 are advantageously short, e.g., at 50° C. Moreover, theresults in Table 2 demonstrate that the crossover values of each of IC1,IC2 and IC3 are advantageously high, e.g., at 50° C. Accordingly, thecompositions of the invention are useful for, e.g., the separation of amixture of biomolecules.

5.3. Preparation of Illustrative Compositions of the InventionComprising PMVA

Two compositions, IC4 and IC5, comprised poly(N-methyl-N-vinylacetamide)(“PMVA”). The weight percent for each of the components present in eachcomposition is provided in Table 3.

TABLE 3 Illustrative Compositions of the Invention Comprising PMVAComposition Designation IC4 IC5 PMVA Mw 1420 kDa 1420 kDa PMVA Amount2.2%  3.0% 10X GA Buffer Amount 9.0%  9.1% Urea Amount 38.0% 38.0%MILLI-Q Water Amount 50.6% 49.9% PDMA^(a) Amount 2.2%   0% ^(a)Mw = 984kDa, Mn = 315 kDa

IC4 was prepared with dialyzed, lyophilized, substantially linear PDMAas described in Example 5.1. The water used in each of IC4-5 waspurified using a MILLI-Q Water System. Each separation medium wasprepared by dissolving, at 25° C., the polymeric components in asolution of buffer and denaturant.

5.4. Capillary Electrophoresis of DNA Using Compositions Comprising PMVA

Illustrative compositions of the invention IC4 and IC5 were evaluatedfor their DNA sequencing performance using CE as described in Example5.2.

The composition and CE sequencing performance data, from an average ofdata from four CE runs, for the separation media are summarized in Table4.

TABLE 4 CE Crossover and Run Time of Compositions of the Invention PMVAPDMA Crossover (bp) Run Time for 700 bp (min) (1420 kDa) (984 kDa) 50°C. 60° C. 70° C. 50° C. 60° C. 70° C. IC4 2.2 wt % 2.2 wt % 546 466 35938.1 36.3 37.7 IC5 3.0 wt % — 550 479 384 46.9 44.7 46.2

The results in Table 4 demonstrate that the run times of each of IC4 andIC5 are advantageously short, e.g., at 50° C. Moreover, the results inTable 4 demonstrate that the crossover values of each of IC4 and IC5 areadvantageously high, e.g., at 50° C. Accordingly, the compositions ofthe invention are useful for, e.g., the separation of a mixture ofbiomolecules.

Although the invention has been described with reference to particularembodiments, it will be appreciated that various changes andmodifications can be made without departing from the spirit or scope ofthe invention.

All concentrations herein are by weight unless otherwise noted.

All publications and patent applications are herein incorporated byreference to the same extent as if each individual publication or patentapplication was specifically and individually indicated to beincorporated by reference.

What is claimed is:
 1. A composition comprising a buffer and a polymerhaving the form poly(M₁ ^(x)M₂ ^(Y)), or a salt thereof, comprising oneor more monomers of type M1 and optionally one or more monomers of typeM₂, wherein: (a) each monomer in the polymer is of type M₁ or M₂; (b) xis an integer ranging from 1 to 5 and represents the number of monomersubtypes of type M₁ that are present in the polymer; (c) y is an integerranging from 0 to 5 and represents the number of monomer subtypes oftype M₂ that are present in the polymer; (d) each monomer subtype oftype M₁ in the polymer is independently: N-vinylformamide,N-vinylacetamide, N-vinylpropamide, N-vinylbutamide, N-vinylpentamide,N-vinylhexamide, N-vinylheptamide, N-vinyloctamide, N-vinylnonamide,N-vinyldecamide, N-methyl-N-vinylformamide, N-methyl-N-vinylacetamide,N-methyl-N-vinylpropamide, N-methyl-N-vinylbutamide,N-methyl-N-vinylpentamide, N-methyl-N-vinylhexamide,N-methyl-N-vinylheptamide, N-methyl-N-vinyloctamide,N-methyl-N-vinylnonamide, N-methyl-N-vinyldecamide,N-ethyl-N-vinylformamide, N-ethyl-N-vinylacetamide,N-ethyl-N-vinylpropamide, N-ethyl-N-vinylbutamide,N-ethyl-N-vinylpentamide, N-ethyl-N-vinylhexamide,N-ethyl-N-vinylheptamide, N-ethyl-N-vinyloctamide,N-ethyl-N-vinylnonamide, N-ethyl-N-vinyldecamide,N-n-propyl-N-vinylformamide, N-n-propyl-N-vinylacetamide,N-n-propyl-N-vinyl propamide, N-n-propyl-N-vinylbutamide,N-n-propyl-N-vinylpentamide, N-n-propyl-N-vinylhexamide,N-n-propyl-N-vinylheptamide, N-n-propyl-N-vinyloctamide,N-n-propyl-N-vinylnonamide, N-n-propyl-N-vinyldecamide,N-iso-propyl-N-vinylformamide, N-iso-propyl-N-vinylacetamide,N-iso-propyl-N-vinylpropamide, N-iso-propyl-N-vinylbutamide,N-iso-propyl-N-vinylpentamide, N-iso-propyl-N-vinylhexamide,N-iso-propyl-N-vinylheptamide, N-isa-propyl-N-vinyloctamide,N-iso-propyl-N-vinylnonamide or N-iso-propyl-N-vinyldecamide; (e) when yis not zero, each monomer subtype of type M₂ in the polymer isindependently: N-hydroxy-acrylamide, N-methoxy-acrylamide, acryloylurea, 1-vinyl-pyrrolidine-2,5-dione, 3-vinyl -oxazolidin-2-one,1-vinyl-imidazolidin-2-one, 4-vinyl-morpholin-3,5-dione,4-vinyl-morpholin-3-one, 4-vinyl-morpholine, 2-vinyl-1,3-dioxolane,2-vinylene carbonate, methoxyethylene, vinyl acetate, vinyl alcohol,acrylamide, N-acetamido-acrylamide, N-acetyl-acrylamide,N-allyl-acrylamide, N-2-aminoethyl-acrylamide hydrochloride,N-2-aminoethyl-N-methyl -acrylamide hydrochloride,N-3-aminopropyl-acrylamide hydrochloride,N-3-aminopropyl-N-methyl-aerylamide hydrochloride,N-butoxymethyl-acrylamide, N-n-butyl-acrylamide,N-tert-butyl-acrylamide, N-2-cyanoethyl-acrylamide,N-cyanomethyl-acrylamide, N-cyanomethyl-N-methyl-acrylamide,N,N-diallyl-acrylamide, N,N-diethyl-acrylamide,N,N-diisopropyl-acrylamide, N,N-dimethyl-acrylamide,N-ethyl-N-methyl-acrylamide, N-ethyl-N-propyl-acrylamide, N-2-glycolicacid-acrylamide, N-2-glycolic acid methyl ester-acrylamide,N-2-hydroxyethyl-acrylamide, N-2-hydroxyethyl-N-methyl-acrylamide,N-hydroxymethyl-acrylamide, N-hydroxymethyl-N-methyl-acrylamide,N-iso-propyl-acrylamide, N-2-methoxyethyl-acrylamide,N-methoxymethyl-acrylamide, N-methyl-acrylamide,N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)methyl-acrylamide,N-tri(hydroxymethyl)methyl-N-methyl-acrylamide,N-3-(trimethylammonium)propyl-acrylamide hydrochloride,N-3-(trimethylammonium)propyl-N-methyl-acrylamide hydrochloride,methacrylamide, N-acetamido-methacrylamide, N-acetyl-methacrylamide,N-allyl-methacrylamide, N-2-aminoethyl-methacrylamide hydrochloride,N-3-aminopropyl-methacrylamide hydrochloride,N-butoxymethyl-methacrylamide, N-n-butyl-methacrylamide,N-tert-butyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N-cyanomethyl-methacrylamide, N-cyanomethyl-N-methyl-methacrylamide,N,N-diethyl-methacrylamide, N,N-dimethyl-methacrylamide, N-2-glycolicacid-methacrylamide, N-2-hydroxyethyl-methacrylamide,N-hydroxymethyl-methacrylamide, N-hydroxymethyl-N-methyl-methacrylamide,N-iso-propyl-methacrylamide, N-2-methoxethyl-methacrylamide,N-methoxymethyl-methacrylamide, N-methyl-methacrylamide,N-tri(hydroxymethyl)methyl-methacrylamide,N-3-(trimethylammonium)propyl-methacrylamide hydrochloride, or a mixturethereof; and (f). further comprises an effective amount of a sieveand/or EOF suppressing polymer comprising a monomer unit that isacrylamide, N-acetyl-acrylamide, N-2-cyanoethyl-acrylamide,N,N-1,2-dihydroxyethylene-bis-acrylamide, N-4,4-dimethoxybutyl-acrylamide, N-2,2-dimethoxyethyl-acrylamide,N,N-dimethyl-acrylamide, N-2-glycolic acid methyl ester acrylamide,N-2-hydroxyethyl-acrylamide, N-hydroxymethyl-acrylamide,N-methoxymethyl-acrylamide, N-3-methoxypropyl-acrylamide,N-methyl-acrylamide, N-methyl-, N-2,2-dimethoxyethyl-acrylamide,N-morpholinoethyl-acrylamide,N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)-methyl-acrylamide, methacrylamide,N-acetyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N,N-1,2-dihydroxyethylene-bis-methacrylamide,N-4,4-dimethoxybutyl-methacrylamide,N-2,2-dimethoxyethyl-methacrylamide, N,N-dimethyl-methacrylamide,N-2-glycolic acid methyl ester methacrylamide,N-2-hydroxyethyl-methacrylamide, N-hydroxymethyl-methacrylamide,N-methoxymethyl-methacrylamide, N-3-methoxypropyl-methacrylamide,N-methyl-methacrylamide, N-methyl-, N-2,2-dimethoxyethyl-methacrylamide,N-morpholinoethyl-methacrylamide,N-2,2,2-trichloro-l-hydroxyethyl-methacrylamide,N-tri(hydroxymethyl)-methyl-methacrylamide, or a mixture thereof.
 2. Thecomposition of claim 1, wherein the sieve and/or EOF suppressing polymermonomer unit is acrylamide.
 3. The composition of claim 1, which furthercomprises an effective amount of a sieve and/or EOF suppressing polymerwhich comprises or is poly(hydroxymethylene), poly(oxyethylene),poly(oxypropylene), poly(oxyethylene-co-oxypropylene),poly(vinylalcohol), poly(vinylpyrrolidone), poly(-ethyl-2-oxazoline),poly(-methyl-2-oxazoline), poly((2-ethyl-2-oxazoline)-co-(2-methyl-2-oxazoline)),poly(N-acetamidoacrylamide), poly(acryloxylurea), hydroxyethylcellulose, hydroxymethyl cellulose, or a mixture thereof.
 4. Thecomposition of claim 1, wherein the polymer has a weight-averagemolecular weight of from about 150,000 Daltons to about 20 MDaltons. 5.The composition of claim 4, which further comprises an effective amountof a sieve and/or EOF suppressing polymer having a weight-averagemolecular weight of from about 1 MDalton to about 5 MDaltons.
 6. Thecomposition of claim 5, wherein the sieve and/or EOF suppressing polymeris substantially linear polyacrylamide.
 7. The composition of claim 1,wherein the composition is an aqueous composition.
 8. The composition ofclaim 7, wherein the composition has a pH of from about 5 to about 11.9. The composition of claim 8, further comprising formamide, urea,pyrrolidone, N-methyl pyrrolidone, or a mixture thereof.
 10. Thecomposition of claim 9, further comprising urea.
 11. The composition ofclaim 9, further comprising formamide.
 12. The composition of claim 7,wherein the composition has a pH of from bout 7 to about
 10. 13. Thecomposition of claim 7, wherein y is 0 and each M1 is independentlyN-vinylformamide or N-methyl-N-vinylacetamide.
 14. The composition ofclaim 1, wherein the composition is a dry composition.
 15. Thecomposition of claim 14, wherein the composition has a pH of from about5 to about
 11. 16. The composition of claim 15, further comprisingformamide, urea, pyrrolidone, N-methyl pyrrolidone, or a mixturethereof.
 17. The composition of claim 16, further comprising urea. 18.The composition of claim 16, further comprising formamide.
 19. Thecomposition of claim 14, wherein the composition has a pH of from about7 to about
 10. 20. The composition of claim 14, wherein y is 0 and eachmonomer subtype of type M₁ is independently N-vinylformamide orN-methyl-N-vinylacetamide.
 21. A capillary containing composition ofclaim 1 comprising a buffer and a polymer having the form poly(M₁ ^(x)M₂^(Y)), or a salt thereof, comprising one or more monomers of type M₁ andoptionally one or more monomers of type M₂, wherein: (a) each monomer inthe polymer is of type M₁ or M₂; (b) x is an integer ranging from 1 to 5and represents the number of monomer subtypes of type M₁ that arepresent in the polymer; (c) y is an integer ranging from 0 to 5 andrepresents the number of monomer subtypes of type M₂ that are present inthe polymer; (d) each monomer subtype of type M₁ in the polymer isindependently: N-vinylformamide, N-vinylacetamide, N-vinylpropamide,N-vinylbutamide, N-vinylpentamide, N-vinylhexamide, N-vinylheptamide,N-vinyloctamide, N-vinylnonamide, N-vinyldecamide,N-methyl-N-vinylformamide, N-methyl-N-vinylacetamide,N-methyl-N-vinylpropamide, N-methyl-N-vinylbutamide,N-methyl-N-vinylpentamide, N-methyl-N-vinylhexamide,N-methyl-N-vinylheptamide, N-methyl-N-vinyloctamide,N-methyl-N-vinylnonamide, N-methyl-N-vinyldecamide,N-ethyl-N-vinylformamide, N-ethyl-N-vinylacetamide,N-ethyl-N-vinylpropamide, N-ethyl-N-vinylbutamide,N-ethyl-N-vinylpentamide, N-ethyl-N-vinylhexamide,N-ethyl-N-vinylheptamide, N-ethyl-N-vinyloctamide,N-ethyl-N-vinylnonamide, N-ethyl-N-vinyldecamide,N-n-propyl-N-vinylformamide, N-n-propyl-N-vinylacetamide,N-n-propyl-N-vinylpropamide, N-n-propyl-N-vinylbutamide,N-n-propyl-N-vinylpentamide, N-n-propyl-N-vinylhexamide,N-n-propyl-N-vinylheptamide, N-n-propyl-N-vinyloctamide,N-n-propyl-N-vinylnonamide, N-n-propyl-N-vinyldecamide,N-iso-propyl-N-vinylformamide, N-iso-propyl-N-vinylacetamide,N-iso-propyl-N-vinylpropamide, N-iso-propyl-N-vinylbutamide,N-iso-propyl-N-vinylpentamide, N-iso-propyl-N-vinylhexamide,N-iso-propyl-N-vinylheptamide, N-isa-propyl-N-vinyloctamide,N-iso-propyl-N-vinylnonamide or N-iso-propyl-N-vinyldecamide; (e) when yis not zero, each monomer subtype of type M₂ in the polymer isindependently: N-hydroxy-acrylamide, N-methoxy-acrylamide, acryloylurea, 1-vinyl-pyrrolidine-2,5-dione, 3-vinyl-oxazolidin-2-one,1-vinyl-imidazoli din-2-one, 4-vinyl-morpholin-3,5-dione,4-vinyl-morpholin-3-one, 4-vinyl-morpholine, 2-vinyl-1,3-dioxolane,2-vinylene carbonate, methoxyethylene, vinyl acetate, vinyl alcohol,acrylamide, N-acetamido-acrylamide, N-acetyl-acrylamide,N-allyl-acrylamide, N-2-aminoethyl-acrylamide hydrochloride,N-2-aminoethyl-N-methyl-acrylamide hydrochloride,N-3-aminopropyl-acrylamide hydrochloride,N-3-aminopropyl-N-methyl-aerylamide hydrochloride,N-butoxymethyl-acrylamide, N-n-butyl-acrylamide,N-tert-butyl-acrylamide, N-2-cyanoethyl-acrylamide,N-cyanomethyl-acrylamide, N-cyanomethyl-N-methyl-acrylamide,N,N-diallyl-acrylamide, N,N-diethyl-acrylamide,N,N-diisopropyl-acrylamide, N,N-dimethyl-acrylamide,N-ethyl-N-methyl-acrylamide, N-ethyl-N-propyl-acrylamide, N-2-glycolicacid-acrylamide, N-2-glycolic acid methyl ester-acrylamide,N-2-hydroxyethyl-acrylamide, N-2-hydroxyethyl-N-methyl-acrylamide,N-hydroxymethyl-acrylamide, N-hydroxymethyl-N-methyl-acrylamide,N-iso-propyl-acrylamide, N-2-methoxyethyl-acrylamide,N-methoxymethyl-acrylamide, N-methyl-acrylamide,N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)methyl-acrylamide,N-tri(hydroxymethyl)methyl-N-methyl-acrylamide,N-3-(trimethylammonium)propyl-acrylamide hydrochloride,N-3-(trimethylammonium)propyl-N-methyl-acrylamide hydrochloride,methacrylamide, N-acetamido-methacrylamide, N-acetyl-methacrylamide,N-allyl-methacrylamide, N-2-aminoethyl-methacrylamide hydrochloride,N-3-aminopropyl-methacrylamide hydrochloride,N-butoxymethyl-methacrylamide, N-n-butyl-methacrylamide,N-tert-butvl-methacrylamide, N-2-cyanoethyl-methacrylamide,N-cyanomethyl-methacrylamide, N-cyanomethyl-N-methyl-methacrylamide,N,N-diethyl-methacrylamide, N,N-dimethyl-methacrylamide, N-2-glycolicacid-methacrylamide, N-2-hydroxyethyl-methacrylamide,N-hydroxymethyl-methacrylamide, N-hydroxymethyl-N-methyl-methacrylamide,N-iso-propyl-methacrylamide, N-2-methoxethyl-methacrylamide,N-methoxymethyl-methacrylamide, N-methyl-methacrylamide,N-tri(hydroxymethyl)methyl-methacrylamide,N-3-(trimethylammonium)propyl-methacrylamide hydrochloride, or a mixturethereof; and (f). further comprises an effective amount of a sieveand/or EOF suppressing polymer comprising a monomer unit that isacrylamide, N-acetyl-acrylamide, N-2-cyanoethyl-acrylamide,N,N-1,2-dihydroxyethylene-bis-acrylamide, N-4,4-dimethoxybutyl1-acrylamide, N-2,2-dimethoxyethyl-acrylamide, N,N-dimethyl-acrylamide,N-2-glycolic acid methyl ester acrylamide, N-2-hydroxyethyl-acrylamide,N-hydroxymethyl-acrylamide, N-methoxymethyl-acrylamide,N-3-methoxypropyl-acrylamide, N-methyl-acrylamide, N-methyl-,N-2,2-dimethoxyethyl-acrylamide, N-morpholinoethyl-acrylamide,N-2,2,2-trichloro-1-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)-methyl-acrylamide, methacrylamide,N-acetyl-methacrylamide, N-2-cyanoethyl-methacrylamide,N,N-1,2-dihydroxyethylene-bis-methacrylamide,N-4,4-dimethoxybutyl-methacrylamide,N-2,2-dimethoxyethyl-methacrylamide, N,N-dimethyl-methacrylamide,N-2-glycolic acid methyl ester methacrylamide,N-2-hydroxyethyl-methacrylamide, N-hydroxymethyl-methacrylamide,N-methoxymethyl-methacrylamide, N-3-methoxypropyl-methacrylamide,N-methyl-methacrylamide, N-methyl-, N-2,2-dimethoxyethyl-methacrylamide,N-morpholinoethyl-methacrylamide, N-2,2,2-trichloro-1-hydroxyethyl-methacrylamide,N-tri(hydroxymethyl)-methyl-methacrylamide, or a mixture thereof. 22.The capillary of claim 21, wherein the capillary is a capillary tube.23. A method for separating a mixture of biomolecules, comprising: (a)contacting the composition of claim 1 with a mixture comprising abiomolecule with a composition comprising a buffer and a polymer havingthe form poly(M₁ ^(x)M₂ ^(Y)), or a salt thereof, comprising one or moremonomers of type M₁ and optionally one or more monomers of type M₂,wherein: (a) each monomer in the polymer is of type M₁ or M₂; (b) x isan integer ranging from 1 to 5 and represents the number of monomersubtypes of type M₁ that are present in the polymer; (c) y is an integerranging from 0 to 5 and represents the number of monomer subtypes oftype M₂ that are present in the polymer; (d) each monomer subtype oftype M₁ in the polymer is independently: N-vinylformamide,N-vinylacetamide, N-vinylpropamide, N-vinylbutamide, N-vinylpentamide,N-vinylhexamide, N-vinylheptamide, N-vinyloctamide, N-vinylnonamide,N-vinyl decamide, N-methyl-N-vinylformamide, N-methyl-N-vinylacetamide,N-methyl-N-vinylpropamide, N-methyl-N-vinylbutamide,N-methyl-N-vinylpentamide, N-methyl-N-vinylhexamide,N-methyl-N-vinylheptamide, N-methyl-N-vinyloctamide,N-methyl-N-vinylnonamide, N-methyl-N-vinyldecamide,N-ethyl-N-vinylformamide, N-ethyl-N-vinylacetamide,N-ethyl-N-vinylpropamide, N-ethyl-N-vinylbutamide,N-ethyl-N-vinylpentamide, N-ethyl-N-vinylhexamide,N-ethyl-N-vinylheptamide, N-ethyl-N-vinyloctamide,N-ethyl-N-vinylnonamide, N-ethyl-N-vinyldecamide,N-n-propyl-N-vinylformamide, N-n-propyl-N-vinylacetamide,N-n-propyl-N-vinylpropamide, N-n-propyl-N-vinylbutamide,N-n-propyl-N-vinylpentamide, N-n-propyl-N-vinylhexamide,N-n-propyl-N-vinylheptamide, N-n-propyl-N-vinyloctamide,N-n-propyl-N-vinylnonamide, N-n-propyl-N-vinyldecamide,N-iso-propyl-N-vinylformamide, N-iso-propyl-N-vinylacetamide,N-iso-propyl-N-vinylpropamide, N-iso-propyl-N-vinylbutamide,N-iso-propyl-N-vinylpentamide, N-iso-propyl-N-vinylhexamide,N-iso-propyl-N-vinylheptamide, N-isa-propyl-N-vinyloctamide,N-iso-propyl-N-vinylnonamide or N-iso-propyl-N-vinyldecamide; and (e)when y is not zero, each monomer subtype of type M₂ in the polymer isindependently: N-hydroxy-acrylamide, N-methoxy-acrylamide, acryloylurea, 1-vinyl-pyrrolidine-2,5-dione, 3-vinyl -oxazolidin-2-one,1-vinyl-imidazolidin-2-one, 4-vinyl-morpholin-3,5-dione,4-vinyl-morpholin-3-one, 4-vinyl-morpholine, 2-vinyl-1,3-dioxolane,2-vinylene carbonate, methoxyethylene, vinyl acetate, vinyl alcohol,acrylamide, N-acetamido-acrylamide, N-acetyl-acrylamide,N-allyl-acrylamide, N-2-aminoethyl-acrylamide hydrochloride,N-2-aminoethyl-N-methyl-acrylamide hydrochloride,N-3-aminopropyl-acrylamide hydrochloride,N-3-aminopropyl-N-methyl-aerylamide hydrochloride,N-butoxymethyl-acrylamide, N-n-butyl-acrylamide,N-tert-butyl-acrylamide, N-2-cyanoethyl-acrylamide,N-cyanomethyl-acrylamide, N-cyanomethyl-N-methyl-acrylamide,N,N-diallyl-acrylamide, N,N-diethyl-acrylamide,N,N-diisopropyl-acrylamide, N,N-dimethyl-acrylamide,N-ethyl-N-methyl-acrylamide, N-ethyl-N-propyl-acrylamide, N-2-glycolicacid-acrylamide, N-2-glycolic acid methyl ester-acrylamide,N-2-hydroxyethyl-acrylamide, N-2-hydroxyethyl-N-methyl-acrylamide,N-hydroxymethyl-acrylamide, N-hydroxymethyl-N-methyl-acrylamide,N-iso-propyl-acrylamide, N-2-methoxyethyl-acrylamide,N-methoxymethyl-acrylamide, N-methyl-acrylamide,N-2,2,2-trichloro-l-hydroxyethyl-acrylamide,N-tri(hydroxymethyl)methyl-acrylamide,N-tri(hydroxymethyl)methyl-N-methyl-acrylamide,N-3-(trimethylammonium)propyl-acrylamide hydrochloride,N-3-(trimethylammonium)propyl-N-methyl-acrylamide hydrochloride,methacrylamide, N-acetamido-methacrylamide, N-acetyl-methacrylamide,N-allyl-methacrylamide, N-2-aminoethyl-methacrylamide hydrochloride,N-3-aminopropyl-methacrylamide hydrochloride,N-butoxymethyl-methacrylamide, N-n-butyl-methacrylamide,N-tert-butvl-methacrylamide, N-2-cyanoethyl-methacrylamide,N-cyanomethyl-methacrylamide, N-cyanomethyl-N-methyl-methacrylamide,N,N-diethyl-methacrylamide, N,N-dimethyl-methacrylamide, N-2-glycolicacid-methacrylamide, N-2-hydroxyethyl-methacrylamide,N-hydroxymethyl-methacrylamide, N-hydroxymethyl-N-methyl-methacrylamide,N-iso-propyl-methacrylamide, N-2-methoxethyl-methacrylamide,N-methoxymethyl-methacrylamide, N-methyl-methacrylamide,N-tri(hydroxymethyl)methyl-methacrylamide,N-3-(trimethylammonium)propyl-methacrylamide hydrochloride, or a mixturethereof; and (b) applying an electric field to the composition in anamount sufficient to facilitate the separation of a biomolecule from themixture.
 24. The method of claim 23, wherein the separation is performedwithin a capillary tube and two or more biomolecules arepolynucleotides.
 25. The method of claim 24, wherein the method forseparating has a crossover of at least about 400 base pairs.